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Sample records for risk hpv11 e7

  1. Characterization of the transport signals that mediate the nucleocytoplasmic traffic of low risk HPV11 E7

    Energy Technology Data Exchange (ETDEWEB)

    McKee, Courtney H.; Onder, Zeynep; Ashok, Aditya; Cardoso, Rebeca; Moroianu, Junona, E-mail: moroianu@bc.edu

    2013-08-15

    We previously discovered that nuclear import of low risk HPV11 E7 is mediated by its zinc-binding domain via a pathway that is independent of karyopherins/importins (Piccioli et al., 2010. Virology 407, 100–109). In this study we mapped and characterized a leucine-rich nuclear export signal (NES), {sub 76}IRQLQDLLL{sub 84}, within the zinc-binding domain that mediates the nuclear export of HPV11 E7 in a CRM1-dependent manner. We also identified a mostly hydrophobic patch {sub 65}VRLVV{sub 69} within the zinc-binding domain that mediates nuclear import of HPV11 E7 via hydrophobic interactions with the FG-repeats domain of Nup62. Substitutions of hydrophobic residues to alanine within the {sub 65}VRLVV{sub 69} sequence disrupt the nuclear localization of 11E7, whereas the R66A mutation has no effect. Overall the data support a model of nuclear entry of HPV11 E7 protein via hydrophobic interactions with FG nucleoporins at the nuclear pore complex. - Highlights: • HPV11 E7 has a leucine-rich nuclear export signal that mediates its nuclear export via CRM1. • HPV11 E7 interacts via its unique cNLS with the FG domain of Nup62. • Identification of a hydrophobic patch essential for nuclear localization of HPV11 E7.

  2. Characterization of the transport signals that mediate the nucleocytoplasmic traffic of low risk HPV11 E7

    International Nuclear Information System (INIS)

    McKee, Courtney H.; Onder, Zeynep; Ashok, Aditya; Cardoso, Rebeca; Moroianu, Junona

    2013-01-01

    We previously discovered that nuclear import of low risk HPV11 E7 is mediated by its zinc-binding domain via a pathway that is independent of karyopherins/importins (Piccioli et al., 2010. Virology 407, 100–109). In this study we mapped and characterized a leucine-rich nuclear export signal (NES), 76 IRQLQDLLL 84 , within the zinc-binding domain that mediates the nuclear export of HPV11 E7 in a CRM1-dependent manner. We also identified a mostly hydrophobic patch 65 VRLVV 69 within the zinc-binding domain that mediates nuclear import of HPV11 E7 via hydrophobic interactions with the FG-repeats domain of Nup62. Substitutions of hydrophobic residues to alanine within the 65 VRLVV 69 sequence disrupt the nuclear localization of 11E7, whereas the R66A mutation has no effect. Overall the data support a model of nuclear entry of HPV11 E7 protein via hydrophobic interactions with FG nucleoporins at the nuclear pore complex. - Highlights: • HPV11 E7 has a leucine-rich nuclear export signal that mediates its nuclear export via CRM1. • HPV11 E7 interacts via its unique cNLS with the FG domain of Nup62. • Identification of a hydrophobic patch essential for nuclear localization of HPV11 E7

  3. The nuclear localization of low risk HPV11 E7 protein mediated by its zinc binding domain is independent of nuclear import receptors

    International Nuclear Information System (INIS)

    Piccioli, Zachary; McKee, Courtney H.; Leszczynski, Anna; Onder, Zeynep; Hannah, Erin C.; Mamoor, Shahan; Crosby, Lauren; Moroianu, Junona

    2010-01-01

    We investigated the nuclear import of low risk HPV11 E7 protein using 1) transfection assays in HeLa cells with EGFP fusion plasmids containing 11E7 and its domains and 2) nuclear import assays in digitonin-permeabilized HeLa cells with GST fusion proteins containing 11E7 and its domains. The EGFP-11E7 and EGFP-11cE7 39-98 localized mostly to the nucleus. The GST-11E7 and GST-11cE7 39-98 were imported into the nuclei in the presence of either Ran-GDP or RanG19V-GTP mutant and in the absence of nuclear import receptors. This suggests that 11E7 enters the nucleus via a Ran-dependent pathway, independent of nuclear import receptors, mediated by a nuclear localization signal located in its C-terminal domain (cNLS). This cNLS contains the zinc binding domain consisting of two copies of Cys-X-X-Cys motif. Mutagenesis of Cys residues in these motifs changed the localization of the EGFP-11cE7/-11E7 mutants to cytoplasmic, suggesting that the zinc binding domain is essential for nuclear localization of 11E7.

  4. HPV-11 variability, persistence and progression to genital warts in men: the HIM study.

    Science.gov (United States)

    Flores-Díaz, Ema; Sereday, Karen A; Ferreira, Silvaneide; Sirak, Bradley; Sobrinho, João Simão; Baggio, Maria Luiza; Galan, Lenice; Silva, Roberto C; Lazcano-Ponce, Eduardo; Giuliano, Anna R; Villa, Luisa L; Sichero, Laura

    2017-09-01

    HPV-11 and HPV-6 are the etiological agents of about 90 % of genital warts (GWs). The intra-typic variability of HPV-11 and its association with infection persistence and GW development remains undetermined. Here, HPV infection in men (HIM) participants who had an HPV-11 genital swab and/or GW, preceded or not by a normal skin genital swab were analysed. Genomic variants were characterized by PCR-sequencing and classified within lineages (A, B) and sublineages (A1, A2, A3, A4). HPV-11 A2 variants were the most frequently detected in the genital swab samples from controls and in both genital swabs and GW samples from cases. The same HPV-11 variant was detected in the GW sample and its preceding genital swab. There was a lack of association between any particular HPV-11 variant and the increased risk for GW development.

  5. Differential expression of cellular microRNAs in HPV 11, -16, and -45 transfected cells

    DEFF Research Database (Denmark)

    Dreher, Anita; Rossing, Maria; Kaczkowski, Bogumil

    2011-01-01

    Human papillomaviruses (HPVs) are highly prevalent giving rise to both benign and malignant lesions why they are classified as high- and low-risk viruses. In this study we selected one low-risk (HPV 11) and two high-risk (HPV 16 and -45) types for genomewide miRNA analysis to investigate possible...

  6. Low- and high-risk human papillomavirus E7 proteins regulate p130 differently

    International Nuclear Information System (INIS)

    Barrow-Laing, Lisa; Chen Wei; Roman, Ann

    2010-01-01

    The E7 protein of high-risk human papillomaviruses (HR HPVs) targets pRb family members (pRb, p107 and p130) for degradation; low-risk (LR) HPV E7 only targets p130 for degradation. The effect of HR HPV 16 E7 and LR HPV 6 E7 on p130 intracellular localization and half-life was examined. Nuclear/cytoplasmic fractionation and immunofluorescence showed that, in contrast to control and HPV 6 E7-expressing cells, a greater amount of p130 was present in the cytoplasm in the presence of HPV 16 E7. The half-life of p130, relative to control cells, was decreased in the cytoplasm in the presence of HPV 6 E7 or HPV 16 E7, but only decreased by HPV 6 E7 in the nucleus. Inhibition of proteasomal degradation extended the half-life of p130, regardless of intracellular localization. These results suggest that there may be divergent mechanisms by which LR and HR HPV E7 target p130 for degradation.

  7. Integrative analyses reveal novel strategies in HPV11,-16 and-45 early infection

    DEFF Research Database (Denmark)

    Kaczkowski, Bogumil; Rossing, Maria; Andersen, Ditte

    2012-01-01

    of genes not previously implicated in HPV biology, such as the PSG family and ANKRD1, and of genes implicated in the biology of other viruses, e. g. MX1, IFI44 and DDX60. Carcinogenesis-related genes, e. g. ABL2, MGLL and CYR61, were upregulated by high-risk HPV16 and -45. The integrative analysis revealed...... the suppression of DNA repair by HPV11 and -16, and downregulation of cytoskeleton genes by all HPV types. Various signalling pathways were affected by the HPVs: IL-2 by HPV11; JAK-STAT by HPV16; and TGF-beta, NOTCH and tyrosine kinase signalling by HPV45. This study uncovered novel strategies employed by HPV...... to establish infection and promote uncontrolled growth....

  8. Evaluation of conflict hazard and financial risk in the E7 economies’ capital markets

    Directory of Open Access Journals (Sweden)

    Ümit Hacıoğlu

    2013-06-01

    Full Text Available The purpose of this research is to examine the interaction between financial stress and conflict risk having impacts on fi nancial instruments in capital markets within an interdisciplinary frame. The Fuzzy TOPSIS method is applied in order to analyse effects of conflict hazard on capital markets and fi nancial instruments in the E7 economies and to demonstrate the best possible ranks of the E7 economies based on performance evaluation criteria. In order to obtain the dynamics of data as to develop a suffi cient reference bases for expert opinions, conflict hazard index and fi nancial stress index have been structured. The empirical results confirm that there is strong relation between fi nancial stress index and confl ict hazard index for the E7 economies. The fundamental conclusion demonstrates the effects of the financial and conflict risks for the stock selection in the E7 economies by the criteria derived from the Financial Stress Index and Confl ict Risk Index.

  9. Human papillomavirus E6 and E7 oncoproteins as risk factors for ...

    Indian Academy of Sciences (India)

    HPV is sexually transmitted and the viral DNA replicates extrachromosomally. The virus is non-enveloped and has an icosahedral capsid. There are approximately 118 types of HPV, which are characterized as high-risk or low-risk types. High-risk HPVs cause malignant transformation while the low-risk ones cause benign ...

  10. Double demonstration of oncogenic high risk human papilloma virus DNA and HPV-E7 protein in oral cancers.

    Science.gov (United States)

    Pannone, G; Santoro, A; Carinci, F; Bufo, P; Papagerakis, S M; Rubini, C; Campisi, G; Giovannelli, L; Contaldo, M; Serpico, R; Mazzotta, M; Lo Muzio, L

    2011-01-01

    Oncogenic HPVs are necessarily involved in cervical cancer but their role in oral carcinogenesis is debated. To detect HPV in oral cancer, 38 cases of formalin fixed-paraffin embedded OSCC were studied by both DNA genotyping (MY09/11 L1 consensus primers in combination with GP5-GP6 primer pair followed by sequencing) and immunohistochemistry (monoclonal Abs against capsid protein and HPV-E7 protein, K1H8 DAKO and clone 8C9 INVITROGEN, respectively). HPV-16 tonsil cancer was used as positive control. The overall prevalence of HPV infection in OSCCs was 10.5%. Amplification of DNA samples showed single HPV DNA infection in 3 cases (HPV16; HPV53; HPV70) and double infection in one case of cheek cancer (HPV31/HPV44). The overall HR-HPV prevalence was 7.5%. E-7 antigen was immunohistochemically detected in all HPV-positive cases. HPV+ OSCC cases showed an overall better outcome than HPV negative oral cancers, as evaluated by Kaplan-Meier curves. HPVs exert their oncogenic role after DNA integration, gene expression of E5, E6 and E7 loci and p53/pRb host proteins suppression. This study showed that HPV-E7 protein inactivating pRb is expressed in oral cancer cells infected by oncogenic HPV other than classical HR-HPV-16/18. Interestingly HPV-70, considered a low risk virus with no definite collocation in oncogenic type category, gives rise to the expression of HPV-E7 protein and inactivate pRb in oral cancer. HPV-70, as proved in current literature, is able to inactivates also p53 protein, promoting cell immortalization. HPV-53, classified as a possible high risk virus, expresses E7 protein in OSCC, contributing to oral carcinogenesis. We have identified among OSCCs, a subgroup characterized by HPV infection (10.5%). Finally, we have proved the oncogenic potential of some HPV virus types, not well known in literature.

  11. High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis.

    Science.gov (United States)

    Yeo-Teh, Nicole S L; Ito, Yoshiaki; Jha, Sudhakar

    2018-06-08

    Infection with high-risk human papillomavirus (HPV) has been linked to several human cancers, the most prominent of which is cervical cancer. The integration of the viral genome into the host genome is one of the manners in which the viral oncogenes E6 and E7 achieve persistent expression. The most well-studied cellular targets of the viral oncogenes E6 and E7 are p53 and pRb, respectively. However, recent research has demonstrated the ability of these two viral factors to target many more cellular factors, including proteins which regulate epigenetic marks and splicing changes in the cell. These have the ability to exert a global change, which eventually culminates to uncontrolled proliferation and carcinogenesis.

  12. Nuclear import of high risk HPV16 E7 oncoprotein is mediated by its zinc-binding domain via hydrophobic interactions with Nup62

    Energy Technology Data Exchange (ETDEWEB)

    Eberhard, Jeremy; Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

    2013-11-15

    We previously discovered that nuclear import of high risk HPV16 E7 is mediated by a cNLS located within the zinc-binding domain via a pathway that is independent of karyopherins/importins (Angeline et al., 2003; Knapp et al., 2009). In this study we continued our characterization of the cNLS and nuclear import pathway of HPV16 E7. We find that an intact zinc-binding domain is essential for the cNLS function in mediating nuclear import of HPV16 E7. Mutagenesis of cysteine residues to alanine in each of the two CysXXCys motifs involved in zinc-binding changes the nuclear localization of the EGFP-16E7 and 2xEGFP-16E7 mutants. We further discover that a patch of hydrophobic residues, {sub 65}LRLCV{sub 69}, within the zinc-binding domain of HPV16 E7 mediates its nuclear import via hydrophobic interactions with the FG domain of the central channel nucleoporin Nup62. - Highlights: • An intact zinc-binding domain is essential for the nuclear localization of HPV16 E7. • Identification of a hydrophobic patch that is critical for the nuclear import of HPV16 E7. • HPV16 E7 interacts via its zinc-binding domain with the FG domain of Nup62.

  13. The E7 oncoprotein of high-risk human papillomavirus type 16 enters the nucleus via a nonclassical Ran-dependent pathway

    International Nuclear Information System (INIS)

    Angeline, Michael; Merle, Eric; Moroianu, Junona

    2003-01-01

    E7, the major transforming protein of high-risk human papillomavirus (HPV), type 16, binds and inactivates the retinoblastoma protein (pRb), and the Rb-related proteins p107 and p130. HPV16 E7 is a nuclear protein lacking a classical basic nuclear localization signal. In this study we investigated the nuclear import of HPV16 E7 oncoprotein in digitonin-permeabilized HeLa cells. HPV16 E7 nuclear import was independent of pRb, as an E7 ΔDLYC variant defective in pRb binding was imported into the nuclei of digitonin-permeabilized cells as efficiently as wild-type E7 in the presence of exogenous cytosol. Interestingly, we discovered that HPV16 E7 is imported into the nuclei via a novel pathway different from those mediated by Kap α2β1 heterodimers, Kap β1, or Kap β2. Nuclear accumulation of E7 required Ran and was not inhibited by the RanG19V-GTP variant, an inhibitor of Kap β mediated import pathways. Together the data suggest that HPV16 E7 translocates through the nuclear pores via a nonclassical Ran-dependent pathway, independent of the main cytosolic Kap β import receptors

  14. Molecular Docking Explains Atomic Interaction between Plant-originated Ligands and Oncogenic E7 Protein of High Risk Human Papillomavirus Type 16

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    Satish Kumar

    2014-12-01

    Full Text Available Cervical cancer caused by Human papillomavirus (HPV is one of the leading causes of cancer mortality in women worldwide, particularly in the developing countries. In the last few decades, various compounds from plant origin such as Curcumin, Epigallocatechin gallate (EGCG, Jaceosidin, Resveratrol etc. have been used as anti cancer therapeutic agents. Different studies have shown these plant-originated compounds are able to suppress HPV infection. The E6 and E7 oncoproteins of high-risk HPV play a key role in HPV related cancers. In this study, we explored these ligands from plants origin against E7 oncoprotein of high risk HPV 16, which is known to inactivate tumor suppressor pRb protein. A robust homology model of HPV 16 E7 was built to foresee the interaction mechanism of E7 oncoprotein with these ligands using structure-based drug designing approach. Docking studies demonstrate the interaction of these ligands with pRb binding site of E7 protein by residues Tyr52, Asn53, Val55, Phe57, Cys59, Ser63, Thr64, Thr72, Arg77, Glu80 and Asp81 and help restoration of pRb functioning. This in silico based atomic interaction between these ligands and E7 protein may assist in validating the plant-originated ligands as effective drugs against HPV.

  15. Differential expression of cellular microRNAs in HPV-11 transfected cells. An analysis by three different array platforms and qRT-PCR

    DEFF Research Database (Denmark)

    Dreher, Anita; Rossing, Maria; Kaczkowski, Bogumil

    2010-01-01

    Human papillomavirus type 11 (HPV-11) infects the genital and the respiratory tract leading to condylomas and respiratory papillomatosis. HPV infections are restricted to epithelial tissue and the progression through the virus lifecycle is tightly coordinated to the differentiation of the host ce...

  16. High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells

    DEFF Research Database (Denmark)

    Bottley, G; Watherston, O G; Hiew, Y-L

    2007-01-01

    a role for E7 in tumour immune evasion. We show that knockdown of E7 expression in HPV16- and HPV18-transformed cervical carcinoma cells by RNA interference increased expression of major histocompatibility complex (MHC) class I at the cell surface and reduced susceptibility of these cells to natural...... killer (NK) cells. Tetracycline-regulated induction of HPV16 E7 resulted in reduced expression of cell surface MHC class I molecules and increased NK cell killing. Our results suggest that, for HPV-associated malignancies, reduced MHC class I expression is the result of an active immune evasion strategy...

  17. HUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E7

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    I. S. Malakhov

    2016-01-01

    Full Text Available The cervical cancer is one of the most common diseases in world. This malignancy is the seventh highest prevalence oncological disease worldwide and the second highest prevalence oncological disease of women in the world. Meanwhile women need to be infected by human papilloma virus (HPV is absolutely necessary for it further evolution, HPV DNA was found in 99.97% cases of disease. Except cervical cancer, HPV cause 85% of rectal cancer, 50% of the vulva, vagina and penis cancers, 20% of oropharyngeal cancer and 10% of larynx and esophagus cancers. In 2009, 14 000 women were diagnosed with cervical cancer in Russia. The growth in morbidity was 19% (in comparison with 1999. The most effective recognised measure for almost each infection prophylaxis is a vaccination. Two human papilloma virus vaccines are available in Russia nowadays — Gardasil and Cervarix, produced in Belgium and the Netherlands respectively. Cervarix is a bivalent vaccine based on virus-like particles (VLP of two types. Recombinant major capsid proteins L1 HPV 16 and HPV 18 express in baculovirus expression system and self-assembled into virus-like particles (about 70 percent of cervical cancers are caused by HPV 16 and HPV 18. VLP of each strain produced in different baculovirus vectors and then combined in single drug. Gardasil is like Cervarix with few exceptions. Producing organisms are fungi S. cerevisiae in this case, and this vaccine contains low-risk HPV 6 and HPV 11 VLP. Thus, Gardasil is quadrivalent HPV-6/11/16/18 vaccine. These vaccines are very effective in averting infection of disease and don’t have significant side-effects, however they have some disadvantages. Firstly, they have a high price because of necessity of their expression in eukaryotic cells. Secondly, they are strain-specific, so vaccines are completely effective only for virus’s strains which are represented in the vaccine. Thirdly, it`s the absence of therapeutic (treatment of established

  18. Monitoring HPV-16 E7 phosphorylation events

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Marcela O.; Hošek, Tomáš; Calçada, Eduardo O.; Castiglia, Francesca [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy); Massimi, Paola; Banks, Lawrence [International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, Trieste (Italy); Felli, Isabella C., E-mail: felli@cerm.unifi.it [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy); Pierattelli, Roberta, E-mail: pierattelli@cerm.unifi.it [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy)

    2017-03-15

    HPV-16 E7 is one of the key proteins that, by interfering with the host metabolism through many protein-protein interactions, hijacks cell regulation and contributes to malignancy. Here we report the high resolution investigation of the CR3 region of HPV-16 E7, both as an isolated domain and in the full-length protein. This opens the way to the atomic level study of the many interactions in which HPV-16 E7 is involved. Along these lines we show here the effect of one of the key post-translational modifications of HPV-16 E7, the phosphorylation by casein kinase II.

  19. Human papillomavirus E6 and E7 oncoproteins alter cell cycle progression but not radiosensitivity of carcinoma cells treated with low-dose-rate radiation

    International Nuclear Information System (INIS)

    DeWeese, Theodore L.; Walsh, Jonathan C.; Dillehay, Larry E.; Kessis, Theodore D.; Hedrick, Lora; Cho, Kathleen R.; Nelson, William G.

    1997-01-01

    Purpose: Low-dose-rate radiation therapy has been widely used in the treatment of urogenital malignancies. When continuously exposed to low-dose-rate ionizing radiation, target cancer cells typically exhibit abnormalities in replicative cell-cycle progression. Cancer cells that arrest in the G2 phase of the cell cycle when irradiated may become exquisitely sensitive to killing by further low-dose-rate radiation treatment. Oncogenic human papillomaviruses (HPVs), which play a major role in the pathogenesis of uterine cervix cancers and other urogenital cancers, encode E6 and E7 transforming proteins known to abrogate a p53-dependent G1 cell-cycle checkpoint activated by conventional acute-dose radiation exposure. This study examined whether expression of HPV E6 and E7 oncoproteins by cancer cells alters the cell-cycle redistribution patterns accompanying low-dose-rate radiation treatment, and whether such alterations in cell-cycle redistribution affect cancer cell killing. Methods and Materials: RKO carcinoma cells, which contain wild-type P53 alleles, and RKO cell sublines genetically engineered to express HPV E6 and E7 oncoproteins, were treated with low-dose-rate (0.25-Gy/h) radiation and then assessed for p53 and p21WAF1/CIP1 polypeptide induction by immunoblot analysis, for cell-cycle redistribution by flow cytometry, and for cytotoxicity by clonogenic survival assay. Results: Low-dose-rate radiation of RKO carcinoma cells triggered p53 polypeptide elevations, p21WAF1/CIP1 induction, and arrest in the G1 and G2 phases of the cell cycle. In contrast, RKO cells expressing E6 and E7 transforming proteins from high-risk oncogenic HPVs (HPV 16) arrested in G2, but failed to arrest in G1, when treated with low-dose-rate ionizing radiation. Abrogation of the G1 cell-cycle checkpoint activated by low-dose-rate radiation exposure appeared to be a characteristic feature of transforming proteins from high-risk oncogenic HPVs: RKO cells expressing E6 from a low-risk

  20. Tinkertoys for the E 7 theory

    Science.gov (United States)

    Chacaltana, Oscar; Distler, Jacques; Trimm, Anderson; Zhu, Yinan

    2018-05-01

    We classify the class S theories of type E 7. These are four-dimensional N=2 superconformal field theories arising from the compactification of the E 7 (2, 0) theory on a punctured Riemann surface, C. The classification is given by listing all 3-punctured spheres ("fixtures"), and connecting cylinders, which can arise in a pants-decomposition of C. We find exactly 11,000 fixtures with three regular punctures, and an additional 48 with one "irregular puncture" (in the sense used in our previous works). To organize this large number of theories, we have created a web application at https://golem.ph.utexas.edu/class-S/E7/. Among these theories, we find 10 new ones with a simple exceptional global symmetry group, as well as a new rank-2 SCFT and several new rank-3 SCFTs. As an application, we study the strong-coupling limit of the E 7 gauge theory with 3 hypermultiplets in the 56. Using our results, we also verify recent conjectures that the T 2 compactification of certain 6 d (1, 0) theories can alternatively be realized in class S as fixtures in the E 7 or E 8 theories.

  1. HPV 11, 16 and 18 DNA sequences in cervical swabs from women with cervical dysplasia: prevalence and associated risk of progression

    DEFF Research Database (Denmark)

    Hørding, U.; Daugaard, S.; Bock, J.E.

    1991-01-01

    Med.mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation......Med.mikrobiologi, papillomavirus, cervical intraepithelial neoplasia, filter in situ hybridisation...

  2. HPV16-E7-Specific Activated CD8 T Cells in E7 Transgenic Skin and Skin Grafts

    Directory of Open Access Journals (Sweden)

    Seyed Davoud Jazayeri

    2017-05-01

    Full Text Available Human papillomavirus (HPV 16 E7 (E7 protein expression in skin promotes epithelial hyperproliferation and transformation to malignancy. Grafts of murine skin expressing E7 protein as a transgene in keratinocytes are not rejected from immunocompetent recipients, whereas grafts expressing ovalbumin (OVA, with or without coexpression of E7 protein, are promptly rejected, demonstrating that E7-associated non-antigen-specific local immunosuppression is not a major determinant of lack of rejection of E7 transgenic skin. To determine whether failure of rejection of E7 skin grafts is due to failure to attract E7-specific effector T cells, E7- and OVA-specific effector CD8+ T cells, activated in vitro, were transferred to animals bearing E7 transgenic skin grafts. Three days after T cell transfer, E7-specific T cells were present in significantly greater numbers than OVA-specific T cells in the grafted skin on animals bearing recently placed or healed E7 grafts, without graft rejection, and also in the ear skin of E7 transgenic animals, without obvious pathology. E7 and OVA-specific T cells were present in lesser numbers in healed E7 grafts than in recently placed grafts and in lesser numbers in recently placed E7 transgenic epidermal grafts without E7-associated hyperproliferation, derived from E7 transgenic mice with a mutated retinoblastoma gene. These data demonstrate that effector T cells are to some extent attracted to E7 transgenic skin specifically by E7 expression, but in large measure non-specifically by the epithelial proliferation associated with E7 expression, and by the local inflammation produced by grafting. Failure of E7 graft rejection was observed despite trafficking of E7-specific effector T cells to E7-expressing epithelium, a finding of consequence for immunotherapy of HPV 16 E7-associated human cancers.

  3. Acute dose and low dose-rate irradiation of carcinoma cells expressing human papillomavirus E6 and E7 oncoproteins - the significance of p53, Rb and G1 arrest status

    International Nuclear Information System (INIS)

    DeWeese, Theodore L.; Walsh, Jonathan C.; Dillehay, Larry E.; Shao, Y.; Kessis, Theodore D.; Cho, Kathleen R.; Nelson, William G.

    1995-01-01

    Purpose: The development of carcinomas in a number of sites including the cervix, vulva and anus have been associated with cellular infection by human papillomaviruses (HPV), including HPV 16 and HPV 18. The mechanism by which these viruses contribute to tumor development or progression seems in part to be related to the integration of the viral genome into the host cells DNA, and the binding of p53 protein by the HPV E6 oncoprotein as well as the binding of the retinoblastoma (Rb) protein and Rb-like proteins by the HPV E7 oncoprotein. These interactions lead to loss of p53 and Rb function including loss of the G 1 cell cycle checkpoint. Although it is believed that both p53 and Rb play a role in the radiosensitivity of the cell, whether alteration in either protein enhances or diminishes cellular radiation response is not clear from the literature. Because HPV-associated tumors such as cervical cancer are often treated with acute dose and/or low dose-rate radiation, we set out to evaluate the radiation response of several carcinoma cell sublines expressing either oncogenic E6 or E7 to both types of radiation, and to determine if p53/Rb dependent G 1 arrest is an important determinant of cell fate after irradiation. Materials and Methods: We have previously developed a series of RKO colorectal carcinoma cell sublines expressing both low-risk (HPV 11) and high-risk (HPV 16) E6 and E7 genes. p53-dependent G 1 arrest is intact in RKO parental cells and cells expressing low-risk E6 proteins, while the G 1 arrest is abrogated in cells expressing high-risk E6 or E7. Clonogenic survival was assessed after exposure to acute dose (1 Gy/min) and low dose-rate (0.25 Gy/hour) radiation. The radiobiologic parameters α, β and the surviving fraction at 2 Gy (SF2) were determined. SDS-PAGE/immunoblotting was carried out to assess both p53 and p21 WAF1/CIP1 levels after exposure to radiation. Flow cytometry was performed before and after exposure to low dose-rate radiation to

  4. The PTPN14 Tumor Suppressor Is a Degradation Target of Human Papillomavirus E7.

    Science.gov (United States)

    Szalmás, Anita; Tomaić, Vjekoslav; Basukala, Om; Massimi, Paola; Mittal, Suruchi; Kónya, József; Banks, Lawrence

    2017-04-01

    Activation of signaling pathways ensuring cell growth is essential for the proliferative competence of human papillomavirus (HPV)-infected cells. Tyrosine kinases and phosphatases are key regulators of cellular growth control pathways. A recently identified potential cellular target of HPV E7 is the cytoplasmic protein tyrosine phosphatase PTPN14, which is a potential tumor suppressor and is linked to the control of the Hippo and Wnt/beta-catenin signaling pathways. In this study, we show that the E7 proteins of both high-risk and low-risk mucosal HPV types can interact with PTPN14. This interaction is independent of retinoblastoma protein (pRb) and involves residues in the carboxy-terminal region of E7. We also show that high-risk E7 induces proteasome-mediated degradation of PTPN14 in cells derived from cervical tumors. This degradation appears to be independent of cullin-1 or cullin-2 but most likely involves the UBR4/p600 ubiquitin ligase. The degree to which E7 downregulates PTPN14 would suggest that this interaction is important for the viral life cycle and potentially also for the development of malignancy. In support of this we find that overexpression of PTPN14 decreases the ability of HPV-16 E7 to cooperate with activated EJ-ras in primary cell transformation assays. IMPORTANCE This study links HPV E7 to the deregulation of protein tyrosine phosphatase signaling pathways. PTPN14 is classified as a potential tumor suppressor protein, and here we show that it is very susceptible to HPV E7-induced proteasome-mediated degradation. Intriguingly, this appears to use a mechanism that is different from that employed by E7 to target pRb. Therefore, this study has important implications for our understanding of the molecular basis for E7 function and also sheds important light on the potential role of PTPN14 as a tumor suppressor. Copyright © 2017 American Society for Microbiology.

  5. [Experimental study on carcinogenesis by human papillomavirus type 8 E7 gene].

    Science.gov (United States)

    Nishikawa, T

    1994-05-01

    Human papillomavirus (HPV) 5 and HPV8 are often detected in skin cancers developed in patients suffering from epidermodysplasia verruciformis, as well as in skin cancers developed in immunosuppressed patients. In the present study, in order to examine the transforming activity of the HPV8E7 gene, the HPV8E7 and HPV8E6/E7 genes were cloned into the expression vector (pcD2-Y), under the SV40 enhancer/promoter to construct pcD2-8E7 and pcD2-8E6/E7, respectively. The E7 and E6/E7 genes of genital high-risk HPV16 were also cloned into pcD2-Y to construct pcD2-16E7 and pcD2-16E6/E7, respectively. They were tested for their ability to collaboratively transform primary rat embryo fibroblasts (REFs) with activated H-ras gene. Transfection experiments of REFs having an activated H-ras gene revealed that pcD2-8E7, as well as pcD2-16E7 and pcD2-16E6/E7, induced transformation of cells in G418-resistant colonies at efficiencies of 11.9%, 43.0% and 53.0%, respectively. Transformed cell lines induced by activated H-ras gene and pcD2-8E7 or pcD2-16E7 were named 8RE and 16RE cell lines, respectively. Tumor induction in syngeneic newborn rats by injected the 8RE cells was higher than that of the 16RE cells. In cytological and histological examination, the 8RE cell lines and their induced tumors were different from the 16RE cell lines and their induced tumors. The 8RE cell lines showed the characteristic transformation with efficient growth ability on plastic and colony formation in 0.3% soft agar. These results support the hypothesis that the HPV8E7 gene plays an important role in the carcinogenesis of skin cancers.

  6. E6 and E7 oncogene expression by human papilloma virus (HPV) and the aggressive behavior of recurrent laryngeal papillomatosis (RLP).

    Science.gov (United States)

    Shehata, Bahig M; Otto, Kristen J; Sobol, Steven E; Stockwell, Christina A; Foulks, Cora; Lancaster, Wayne; Gregoire, Lucie; Hill, Charles E

    2008-01-01

    Recurrent laryngeal papillomatosis (RLP), a chronic disease associated with human papilloma virus (HPV), requires serial surgical procedures for debulking, resulting in debilitating long-term dysphonia, laryngeal scarring, and rarely malignant degeneration. Human papilloma virus 11 tumors have been widely accepted as more aggressive than HPV 6 tumors; however, the clinical course has been difficult to predict at disease onset, and the biologic mediators of proliferation have not been well characterized. A retrospective case review of 43 patients (4 months to 10 years at diagnosis) was performed on children treated for recurrent laryngeal papillomatosis. Patient charts were reviewed for demographic information, age at RLP diagnosis, approximate frequency of surgical intervention, and absolute number of surgical procedures performed. Human papilloma virus subtyping was performed. Expression analysis of the HPV-encoded E6 and E7 oncogenes was performed by reverse-transcriptase polymerase chain reaction. Fourteen patients had subtype 11 (33%) and 29 patients had subtype 6 (67%). As expected, HPV 11 patients showed a more aggressive clinical course than HPV 6 patients. However, 38% of patients with subtype 6 (11 patients) followed a clinical course that mirrored the more severe subtype 11 patients. These patients expressed the disease at a younger age (P < 0.0002) and showed higher levels of E6 and E7 oncogenes compared to the patients with the more indolent course. Although HPV subtype and early onset of RLP are well characterized prognostic factors, our study documents the significance of E6 and E7 oncogene expression as potential biologic mediators of proliferation and thereby clinical behavior.

  7. Simultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation

    DEFF Research Database (Denmark)

    Kaznelson, Dorte Wissing; Bruun, Silas; Monrad, Astrid

    2004-01-01

    Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation and induc......Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation......, possibly because of conflicting growth control. Interestingly, E7/p21-induced cell death is associated with the activation of a newly identified mediator of apoptosis, namely cathepsin B. Activation of the cellular caspases is undetectable in cells undergoing E7/p21-induced apoptosis. To our knowledge...

  8. The human papillomavirus type 58 E7 oncoprotein modulates cell cycle regulatory proteins and abrogates cell cycle checkpoints

    International Nuclear Information System (INIS)

    Zhang Weifang; Li Jing; Kanginakudru, Sriramana; Zhao Weiming; Yu Xiuping; Chen, Jason J.

    2010-01-01

    HPV type 58 (HPV-58) is the third most common HPV type in cervical cancer from Eastern Asia, yet little is known about how it promotes carcinogenesis. In this study, we demonstrate that HPV-58 E7 significantly promoted the proliferation and extended the lifespan of primary human keratinocytes (PHKs). HPV-58 E7 abrogated the G1 and the postmitotic checkpoints, although less efficiently than HPV-16 E7. Consistent with these observations, HPV-58 E7 down-regulated the cellular tumor suppressor pRb to a lesser extent than HPV-16 E7. Similar to HPV-16 E7 expressing PHKs, Cdk2 remained active in HPV-58 E7 expressing PHKs despite the presence of elevated levels of p53 and p21. Interestingly, HPV-58 E7 down-regulated p130 more efficiently than HPV-16 E7. Our study demonstrates a correlation between the ability of down-regulating pRb/p130 and abrogating cell cycle checkpoints by HPV-58 E7, which also correlates with the biological risks of cervical cancer progression associated with HPV-58 infection.

  9. Dominant Role of HPV16 E7 in Anal Carcinogenesis

    Science.gov (United States)

    Thomas, Marie K.; Pitot, Henry C.; Liem, Amy; Lambert, Paul F.

    2011-01-01

    Ninety percent of anal cancer is associated with human papilloma viruses (HPVs). Using our previously established HPV transgenic mouse model for anal cancer, we tested the role of the individual oncogenes E6 and E7. K14E6 and K14E7 transgenic mice were treated with dimethylbenz[a]anthracene (DMBA) to the anal canal and compared to matched nontransgenic and doubly transgenic K14E6/E7 mice. K14E7 and K14E6/E7 transgenic mice developed anal tumors (papillomas, atypias and carcinomas combined) at significantly higher rates (88% and 100%, respectively) than either K14E6 or NTG mice (18% and 19%, respectively). Likewise, K14E7 and K14E6/E7 transgenic mice developed frank cancer (carcinomas) at significantly higher rates (85% and 85%, respectively) than either K14E6 or NTG mice (18% and 10%, respectively). These findings indicate that E7 is the more potent oncogene in anal cancer caused by HPVs. PMID:21999991

  10. Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice

    International Nuclear Information System (INIS)

    Whitehead, Mark; Öhlschläger, Peter; Almajhdi, Fahad N; Alloza, Leonor; Marzábal, Pablo; Meyers, Ann E; Hitzeroth, Inga I; Rybicki, Edward P

    2014-01-01

    Human papillomaviruses (HPV) are the causative agents of cervical cancer in women, which results in over 250 000 deaths per year. Presently there are two prophylactic vaccines on the market, protecting against the two most common high-risk HPV types 16 and 18. These vaccines remain very expensive and are not generally affordable in developing countries where they are needed most. Additionally, there remains a need to treat women that are already infected with HPV, and who have high-grade lesions or cervical cancer. In this paper, we characterize the immunogenicity of a therapeutic vaccine that targets the E7 protein of the most prevalent high-risk HPV - type 16 – the gene which has previously been shown to be effective in DNA vaccine trials in mice. The synthetic shuffled HPV-16 E7 (16E7SH) has lost its transforming properties but retains all naturally-occurring CTL epitopes. This was genetically fused to Zera®, a self-assembly domain of the maize γ-zein able to induce the accumulation of recombinant proteins into protein bodies (PBs), within the endoplasmic reticulum in a number of expression systems. High-level expression of the HPV 16E7SH protein fused to Zera® in plants was achieved, and the protein bodies could be easily and cost-effectively purified. Immune responses comparable to the 16E7SH DNA vaccine were demonstrated in the murine model, with the protein vaccine successfully inducing a specific humoral as well as cell mediated immune response, and mediating tumour regression. The fusion of 16E7SH to the Zera® peptide was found to enhance the immune responses, presumably by means of a more efficient antigen presentation via the protein bodies. Interestingly, simply mixing the free PBs and 16E7SH also enhanced immune responses, indicating an adjuvant activity for the Zera® PBs

  11. Activities of E7 promoters in the human papillomavirus type 16 genome during cell differentiation

    DEFF Research Database (Denmark)

    Hansen, Christina Neigaard; Nielsen, Lone; Norrild, Bodil

    2010-01-01

    Worldwide, one of the most common cancer forms diagnosed in women is cervical cancer induced by infections with high-risk human papillomaviruses (HPVs) with HPV type 16 (HPV-16) being the most frequently identified. The oncogenicity is caused mainly by expression of the oncogenes E6 and E7 leadin...

  12. Detection of E6/E7 HPV oncogene transcripts as biomarker of cervical intaepithelial displasia

    Directory of Open Access Journals (Sweden)

    Mauro Carcheri

    2009-09-01

    Full Text Available It is widely accepted that only persistent infection with high risk types of Human Papillomavirus (HPV HR is a significant risk factor for the development of an invasive squamous cervical cancer. The overexpression of viral oncogenes E6/E7 of HPV is considered a necessary process for incurring in a malignant phenotype.A HPV infection can be identified by detection of HPV DNA in biological samples, but the DNAbased tests cannot delineate between transient or persistent and potentially transforming infection. Instead there is many evidence to suggest that detection of HPV gene expression may constitute a more specific approach to highlight a clinically significant infection. Especially seems that the detection of E6/E7 transcripts can be usefully used for identify the women with a persistent HPV infection that will can induce a future cervical cancer. The aim of our study is to investigate if the detection of oncogenic viral gene activity by detecting transcripts of the E6 and E7 genes can be most usefull of HPV-DNA test in the triage of ASCUS or low grade cervical lesions. Our results confirm that HPV E6/E7 mRNA test can be considered a promising method to stratify HPV positive women for risk of future high-grade cervical lesions or cervical intaepithelial neoplasia.

  13. High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology

    Science.gov (United States)

    Rijkaart, D. C.; Heideman, D. A. M.; Coupe, V. M. H.; Brink, A. A. T. P.; Verheijen, R. H. M.; Skomedal, H.; Karlsen, F.; Morland, E.; Snijders, P. J. F.

    2012-01-01

    Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy. PMID:22553244

  14. human papillomaviruses E6 and E7 oncoproteins

    Indian Academy of Sciences (India)

    Unknown

    Recent work has uncovered new cellular partners for these .... Hence it is evident that a fine balance exists between these that govern ... still suggest that E7 can have a more global effect on the general .... towards malignancy), increases life span of the cells. E6 ..... nism when expressed alone in HPV positive/negative cell.

  15. Globalization and sustainable development an E7 point of view

    Energy Technology Data Exchange (ETDEWEB)

    Strassburg, W.

    1998-07-01

    The energy sector is a crucial feedstock to economic development. One example of this industry sector's contribution towards sustainable development is the so-called E7 initiative on sustainable energy development of some of the biggest electric utilities. E7 members from Canada, France, Germany, Italy, Japan and the US are demonstrating the functioning of the requested globally synchronized approach between developed and developing countries. E7 members focus their activities on (1) the efficient use of primary energy resources, (2) maximizing the use of renewable energy resources, (3) maximizing efficiency in the generation, delivery, and use of electricity, (4) minimizing environmental impacts of energy production and use and, (5) implementing innovative options to promote win-win benefits for the environment and the economy through their network of expertise on a pro bono basis. A main emphasis lies in the consistent Joint Implementation given the fact that innovative and efficient Green House Gas reduction measures will be the core of future E7 activities. Especially commercial projects will provide valuable contributions to Green House Gas reductions as well as to economic development of the recipient country. Other instruments, such Emission Trading and Clean Development Mechanism will have to be investigated appropriately in terms of their practicability for Green House Gas reductions so that their will be a notification by the international climate protection regime. Therefore Emission Trading and Clean Development Mechanism are of importance for E7 members' future operations, too. With respect to Sustainable Development industry, energy and environmental policy in leading industry countries must be more closely aligned to a global approach than has so far been the case. The electricity sector is called on to make a major contribution.

  16. Simultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation

    International Nuclear Information System (INIS)

    Kaznelson, Dorte Wissing; Bruun, Silas; Monrad, Astrid; Gjerloev, Simon; Birk, Jesper; Roepke, Carsten; Norrild, Bodil

    2004-01-01

    Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation and induction of cell death. We have used the osteosarcoma cell line U2OS cells provided with E7 and the cdk2 inhibitor p21 (cip1/waf1) under inducible control, as a model system for the analysis of E7-mediated apoptosis. Our data shows that simultaneous expression of E7 and p21 proteins induces cell death, possibly because of conflicting growth control. Interestingly, E7/p21-induced cell death is associated with the activation of a newly identified mediator of apoptosis, namely cathepsin B. Activation of the cellular caspases is undetectable in cells undergoing E7/p21-induced apoptosis. To our knowledge, this is the first time a role for cathepsin B is reported in HPV-induced apoptotic signalling

  17. The Subcellular Localisation of the Human Papillomavirus (HPV 16 E7 Protein in Cervical Cancer Cells and Its Perturbation by RNA Aptamers

    Directory of Open Access Journals (Sweden)

    Özlem Cesur

    2015-06-01

    Full Text Available Human papillomavirus (HPV is the most common viral infection of the reproductive tract, affecting both men and women. High-risk oncogenic types are responsible for almost 90% of anogenital and oropharyngeal cancers including cervical cancer. Some of the HPV “early” genes, particularly E6 and E7, are known to act as oncogenes that promote tumour growth and malignant transformation. Most notably, HPV-16 E7 interacts with the tumour suppressor protein pRb, promoting its degradation, leading to cell cycle dysregulation in infected cells. We have previously shown that an RNA aptamer (termed A2 selectively binds to HPV16 E7 and is able to induce apoptosis in HPV16-transformed cervical carcinoma cell lines (SiHa through reduction of E7 levels. In this study, we investigated the effects of the A2 aptamer on E7 localisation in order to define its effects on E7 activity. We demonstrate for the first time that E7 localised to the plasma membrane. In addition, we show that A2 enhanced E7 localisation in the ER and that the A2-mediated reduction of E7 was not associated with proteasomal degradation. These data suggest that A2 perturbs normal E7 trafficking through promoting E7 ER retention.

  18. E(7) symmetric area of the black hole horizon

    International Nuclear Information System (INIS)

    Kallosh, R.; Kol, B.

    1996-01-01

    Extreme black holes with 1/8 of unbroken N=8 supersymmetry are characterized by the nonvanishing area of the horizon. The central charge matrix has four generic eigenvalues. The area is proportional to the square root of the invariant quartic form of E 7(7) . It vanishes in all cases when 1/4 or 1/2 of supersymmetry is unbroken. The supergravity nonrenormalization theorem for the area of the horizon in the N=8 case protects the unique U-duality invariant. copyright 1996 The American Physical Society

  19. Cervical Cancers Require the Continuous Expression of the Human Papillomavirus Type 16 E7 Oncoprotein Even in the Presence of the Viral E6 Oncoprotein

    Science.gov (United States)

    Jabbar, Sean F.; Park, Soyeong; Schweizer, Johannes; Berard-Bergery, Marthe; Pitot, Henry C.; Lee, Denis; Lambert, Paul F.

    2012-01-01

    High-risk human papillomaviruses (HPV), such as HPV-16, are etiologic agents of a variety of anogenital and oral malignancies, including nearly all cases of cervical cancer. Cervical cancers arising in transgenic mice that express HPV-16 E7 in an inducible manner require the continuous expression of E7 for their maintenance. However, in HPV-associated cancers in vivo, E6 and E7 invariably are co-expressed. In this study, we investigated whether cervical cancers rely on the continuous expression of E7 in the context of constitutively expressed E6. We placed the inducible HPV-16 E7 transgene onto a background in which HPV-16 E6 was constitutively expressed. In transgenic mice with high-grade cervical dysplastic lesions and cervical cancer, repressing the expression of E7 led to the regression of all cancers and the vast majority of high-grade dysplastic lesions. In addition, cervical cancers were occasionally observed in transgenic mice in which E7 was repressed and then re-expressed. Our findings therefore indicate that even in the presence of constitutively expressed E6, the continuous expression of E7 is required for the maintenance of cervical cancers and most precancerous lesions. These data have important implications for the potential clinical use of drugs designed to inhibit the expression and/or function of E7 to treat HPV-associated cancers. PMID:22700879

  20. The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression

    Directory of Open Access Journals (Sweden)

    Duensing Stefan

    2011-05-01

    Full Text Available Abstract Background Infection with high-risk human papillomaviruses (HPVs such as HPV-16 is intimately associated with squamous cell carcinomas (SCCs of the anogenital tract and a subset of oropharyngeal carcinomas. Such lesions, including pre-invasive precursors, frequently show multipolar mitoses and aneuploidy. The high-risk HPV-16-encoded E7 oncoprotein has been shown to rapidly induce centrosome abnormalities thereby causing the formation of supernumerary mitotic spindle poles and increasing the risk for chromosome missegregation. HPV-16 E7 has been found to rapidly induce centriole overduplication, in part, through the simultaneous formation of more than one daughter centriole at single maternal centrioles (centriole multiplication. The precise molecular mechanism that underlies HPV-16 E7-induced centriole multiplication, however, remains poorly understood. Findings Here, we show that human keratinocytes engineered to stably express the HPV-16 E7 oncoprotein exhibit aberrant Polo-like kinase 4 (PLK4 protein expression at maternal centrioles. Real-time quantitative reverse transcriptase (qRT-PCR analysis of these cells revealed an increase of PLK4 mRNA levels compared to control cells. Importantly, the ability of the HPV-16 E7 oncoprotein to induce centriole multiplication was found to correlate with its ability to activate the PLK4 promoter and to up-regulate PLK4 mRNA. Conclusions These results highlight the critical role of PLK4 transcriptional deregulation in centriole multiplication in HPV-16 E7-expressing cells. Our findings encourage further experiments to test transcriptional inhibitors or small molecules targeting PLK4 to prevent centriole abnormalities, mitotic infidelity and malignant progression in HPV-associated neoplasms and other tumors in which PLK4 regulation is disrupted.

  1. E6 and E7 Gene Polymorphisms in Human Papillomavirus Types-58 and 33 Identified in Southwest China.

    Directory of Open Access Journals (Sweden)

    Zuyi Chen

    Full Text Available Cancer of the cervix is associated with infection by certain types of human papillomavirus (HPV. The gene variants differ in immune responses and oncogenic potential. The E6 and E7 proteins encoded by high-risk HPV play a key role in cellular transformation. HPV-33 and HPV-58 types are highly prevalent among Chinese women. To study the gene intratypic variations, polymorphisms and positive selections of HPV-33 and HPV-58 E6/E7 in southwest China, HPV-33 (E6, E7: n = 216 and HPV-58 (E6, E7: n = 405 E6 and E7 genes were sequenced and compared to others submitted to GenBank. Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by MEGA 6 (Molecular Evolutionary Genetics Analysis version 6.0. The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by PAML 4.8 (Phylogenetic Analyses by Maximun Likelihood version4.8 software. The positive sites of HPV-33 and HPV-58 E6/E7 were contrasted by ClustalX 2.1. Among 216 HPV-33 E6 sequences, 8 single nucleotide mutations were observed with 6/8 non-synonymous and 2/8 synonymous mutations. The 216 HPV-33 E7 sequences showed 3 single nucleotide mutations that were non-synonymous. The 405 HPV-58 E6 sequences revealed 8 single nucleotide mutations with 4/8 non-synonymous and 4/8 synonymous mutations. Among 405 HPV-58 E7 sequences, 13 single nucleotide mutations were observed with 10/13 non-synonymous mutations and 3/13 synonymous mutations. The selective pressure analysis showed that all HPV-33 and 4/6 HPV-58 E6/E7 major non-synonymous mutations were sites of positive selection. All variations were observed in sites belonging to major histocompatibility complex and/or B-cell predicted epitopes. K93N and R145 (I/N were observed in both HPV-33 and HPV-58 E6.

  2. HPV E6 and E7 in hypoxia mediated tumorigenesis in cervical epithelial cells

    International Nuclear Information System (INIS)

    Kim, Charlotte Y.; Tsai, Mitchell; Graeber, Thomas G.; Peehl, Donna M.; Giaccia, Amato J.

    1996-01-01

    Objective: In our previous work, we found that hypoxia induces apoptosis in oncogenically transformed rodent cells and loss of the p53 tumor suppressor gene significantly reduces hypoxia induced cell death. In this report, we show that transformation of wild-type p53 expressing primary cervical epithelial cells with the E6 and E7 genes from high risk human papillomavirus (HPV) type 16 dramatically enhances their susceptibility to hypoxia induced apoptosis. Materials and Methods: Sub confluent primary normal human cervical epithelial cells and normal human fibroblasts were infected with retroviral vectors containing HPV16 E6 and E7 and the neomycin selectable marker using previously described techniques. Clones were selected and isolated in neomycin containing media. Exponentially growing cells were treated with hypoxia (0.02% O 2 ) using specially designed chambers, irradiated (800 cGy) using a cesium source, or grown under aerobic conditions (20% O 2 ) as a control. After treatment, cells were stained with Hoescht and propidium iodide and viewed with a fluorescent microscope for analysis of apoptotic cells. To determine increase in expression of p53, immuno blots were performed using whole cell extracts. Results: After a 48 hour exposure to hypoxic conditions, 40% of E6 and E7 transformed cervical cells exhibit morphologic features indicative of apoptosis, compared to 5% of untransformed cervical cells. Exposure of HPV E6 and E7 transformed cells to ionizing radiation, however, did not initiate apoptosis. Immunoblot assays show induction of p53 under hypoxic conditions but not by ionizing radiation, indicating that hypoxia is able to induce p53 in the presence of E6 and that hypoxia activates p53 by a pathway which is distinct from that of ionizing radiation. Furthermore, hypoxia did not induce apoptosis in normal human fibroblasts transformed with E6 and E7, suggesting that the cellular response to hypoxia is influenced by the cell type. Conclusion: These results

  3. Genetic variability in E6 and E7 oncogenes of human papillomavirus Type 16 from Congolese cervical cancer isolates

    OpenAIRE

    Boumba, Luc Magloire Anicet; Assoumou, Samira Zoa; Hilali, Lahoucine; Mambou, Jean Victor; Moukassa, Donatien; Ennaji, Mustapha Moulay

    2015-01-01

    Background The molecular epidemiological studies showed that some variants of HPV-16, distributed geographically, would present a higher risk of causing cervical cancer. This study aimed to analyze nucleotide changes of HPV-16 E6 and E7 genomic regions from infected Southwestern Congolese women. Methods DNA of twenty HPV-16 isolates was analyzed by amplifying the E6 and E7 genes using type-specific primers PCR and direct sequencing. The sequences obtained were aligned with the HPV-16 GenBank ...

  4. Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57/BL6 mice.

    Science.gov (United States)

    Poo, Haryoung; Pyo, Hyun-Mi; Lee, Tae-Young; Yoon, Sun-Woo; Lee, Jong-Soo; Kim, Chul-Joong; Sung, Moon-Hee; Lee, Seung-Hoon

    2006-10-01

    The mounting of a specific immune response against the human papillomavirus type 16 E7 protein (HPV16 E7) is important for eradication of HPV16 E7-expressing cancer cells from the cervical mucosa. To induce a mucosal immune response by oral delivery of the E7 antigen, we expressed the HPV16 E7 antigen on the surface of Lactobacillus casei by employing a novel display system in which the poly-gamma-glutamic acid (gamma-PGA) synthetase complex A (PgsA) from Bacillus subtilis (chungkookjang) was used as an anchoring motif. After surface expression of the HPV16 E7 protein was confirmed by Western blot, flow cytometry and immunofluorescence microscopy, mice were orally inoculated with L. casei-PgsA-E7. E7-specific serum IgG and mucosal IgA productions were enhanced after oral administration and significantly enhanced after boosting. Systemic and local cellular immunities were significantly increased after boosting, as shown by increased counts of lymphocytes (SI = 9.7 +/- 1.8) and IFN-gamma secreting cells [510 +/- 86 spot-forming cells/10(6)cells] among splenocytes and increased IFN-gamma in supernatants of vaginal lymphocytes. Furthermore, in an E7-based mouse tumor model, animals receiving orally administered L. casei-PgsA-E7 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei-PgsA) immunization. These results collectively indicate that the oral administration of E7 displayed on lactobacillus induces cellular immunity and antitumor effects in mice. Copyright 2006 Wiley-Liss, Inc.

  5. Retinoblastoma-independent antiproliferative activity of novel intracellular antibodies against the E7 oncoprotein in HPV 16-positive cells

    International Nuclear Information System (INIS)

    Accardi, Luisa; Tommasino, Massimo; Banks, Lawrence; Chirullo, Barbara; Giorgi, Colomba; Donà, Maria Gabriella; Mileo, Anna M; Paggi, Marco G; Federico, Antonio; Torreri, Paola; Petrucci, Tamara C; Accardi, Rosita; Pim, David

    2011-01-01

    'High risk' Human Papillomavirus strains are the causative agents of the vast majority of carcinomas of the uterine cervix. In these tumors, the physical integration of the HPV genome is a frequent, though not invariable occurrence, but the constitutive expression of the E6 and E7 viral genes is always observed, suggesting key roles for the E6 and E7 oncoproteins in the process of malignant transformation. The 'intracellular antibody' technology using recombinant antibodies in single-chain format offers the possibility of targeting a protein in its intracellular environment even at the level of definite domains thus representing a valuable strategy to 'knock out' the function of specific proteins. In this study, we investigate the in vitro activity of two single-chain antibody fragments directed against the 'high-risk' HPV 16 E7 oncoprotein, scFv 43M2 and scFv 51. These scFvs were expressed by retroviral system in different cell compartments of the HPV16-positive SiHa cells, and cell proliferation was analyzed by Colony Formation Assay and EZ4U assay. The binding of these scFvs to E7, and their possible interference with the interaction between E7 and its main target, the tumor suppressor pRb protein, were then investigated by immunoassays, PepSet™technology and Surface Plasmon Resonance. The expression of the two scFvs in the nucleus and the endoplasmic reticulum of SiHa cells resulted in the selective growth inhibition of these cells. Analysis of binding showed that both scFvs bind E7 via distinct but overlapping epitopes not corresponding to the pRb binding site. Nevertheless, the binding of scFv 43M2 to E7 was inhibited by pRb in a non-competitive manner. Based on the overall results, the observed inhibition of HPV-positive SiHa cells proliferation could be ascribed to an interaction between scFv and E7, involving non-pRb targets. The study paves the way for the employment of specific scFvs in immunotherapeutic

  6. Disruption of HPV16-E7 by CRISPR/Cas System Induces Apoptosis and Growth Inhibition in HPV16 Positive Human Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Zheng Hu

    2014-01-01

    Full Text Available High-risk human papillomavirus (HR-HPV has been recognized as a major causative agent for cervical cancer. Upon HPV infection, early genes E6 and E7 play important roles in maintaining malignant phenotype of cervical cancer cells. By using clustered regularly interspaced short palindromic repeats- (CRISPR- associated protein system (CRISPR/Cas system, a widely used genome editing tool in many organisms, to target HPV16-E7 DNA in HPV positive cell lines, we showed for the first time that the HPV16-E7 single-guide RNA (sgRNA guided CRISPR/Cas system could disrupt HPV16-E7 DNA at specific sites, inducing apoptosis and growth inhibition in HPV positive SiHa and Caski cells, but not in HPV negative C33A and HEK293 cells. Moreover, disruption of E7 DNA directly leads to downregulation of E7 protein and upregulation of tumor suppressor protein pRb. Therefore, our results suggest that HPV16-E7 gRNA guided CRISPR/Cas system might be used as a therapeutic strategy for the treatment of cervical cancer.

  7. Design of a colicin E7 based chimeric zinc-finger nuclease

    Science.gov (United States)

    Németh, Eszter; Schilli, Gabriella K.; Nagy, Gábor; Hasenhindl, Christoph; Gyurcsik, Béla; Oostenbrink, Chris

    2014-08-01

    Colicin E7 is a natural bacterial toxin. Its nuclease domain (NColE7) enters the target cell and kills it by digesting the nucleic acids. The HNH-motif as the catalytic centre of NColE7 at the C-terminus requires the positively charged N-terminal loop for the nuclease activity—offering opportunities for allosteric control in a NColE7-based artificial nuclease. Accordingly, four novel zinc finger nucleases were designed by computational methods exploiting the special structural features of NColE7. The constructed models were subjected to MD simulations. The comparison of structural stability and functional aspects showed that these models may function as safely controlled artificial nucleases. This study was complemented by random mutagenesis experiments identifying potentially important residues for NColE7 function outside the catalytic region.

  8. The e7 guide to implementing projects under the Clean Development Mechanism

    International Nuclear Information System (INIS)

    2003-09-01

    The e7 was formed in 1992 to play an active role in global electricity issues and to promote sustainable development. It consists of nine leading electricity companies: American Electric Power (United States), Electricite de France (France), ENEL (Italy), Hydro-Quebec (Canada), The Kansai Electric Power Company, Inc. (Japan), Ontario Power Generation, Inc. (Canada), RWE (Germany), ScottishPower (United Kingdom), and Tokyo Electric Power Company (Japan). This report provides a guide to help develop projects under the Clean Development Mechanism (CDM), which is an instrument that allows public or private entities to invest in greenhouse gas (GHG) mitigating activities in developing countries and earn credits in an emission trading system. The dual objectives of the CDM, one of three mechanisms set out in the Kyoto Protocol, are the reduction of global GHG emissions and a contribution to sustainable development in the host country. The guidelines and procedures detailed by the United Nations Framework Convention on Climate Change (UN FCCC) and the related Protocols and Accords, were followed in the preparation of this document. Recommendations based on e7 experience were also included. The criteria for success were stated, and additionality was discussed. Additionality refers to the reductions of emissions that are additional to any that would occur in the absence of the certified project activity. The baseline methodology was described. Project Design Document (PDD) is the format that must be used for presenting the information pertaining to a project and its evaluation. PDD contents include: general description of the project activity, baseline methodology, identification of crediting period, monitoring methodology and plan, calculation of GHG emissions by sources, environmental impacts, and stakeholder comments. Third party verification, and project risk and transaction costs were also addressed. refs., tabs., figs

  9. 77 FR 9948 - International Conference on Harmonisation; Guidance on E7 Studies in Support of Special...

    Science.gov (United States)

    2012-02-21

    ...] International Conference on Harmonisation; Guidance on E7 Studies in Support of Special Populations; Geriatrics... Food and Drug Administration (FDA) is announcing the availability of a guidance entitled ``E7 Studies... under the auspices of the International Conference on Harmonisation of Technical Requirements for...

  10. Production of recombinant proteins GST L1, E6 and E7 tag HPV 16 ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-02-04

    Feb 4, 2009 ... targeting the viral oncoproteins E6 and E7 are markers for HPV-associated ... Luminex XYP plate handler, Luminex SD sheath fluid delivery system, a Pentium 4 .... expression mediated by a potato virus X derived vector of the E7 protein .... inflammation, and antioxidant nutrients – assessing their roles as.

  11. A prime/boost strategy by DNA/fowlpox recombinants expressing a mutant E7 protein for the immunotherapy of HPV-associated cancers.

    Science.gov (United States)

    Radaelli, Antonia; De Giuli Morghen, Carlo; Zanotto, Carlo; Pacchioni, Sole; Bissa, Massimiliano; Franconi, Rosella; Massa, Silvia; Paolini, Francesca; Muller, Antonio; Venuti, Aldo

    2012-12-01

    Development of effective therapeutic vaccines against human papilloma virus (HPV) infections remains a priority, considering the high number of new cases of cervical cancer each year by high-risk HPVs, in particular by HPV-16. Vaccines expressing the E7 oncoprotein, which is detectable in all HPV-positive pre-cancerous and cancer cells, might clear already established tumors and support the treatment of HPV-related lesions. In this study, DNA or fowlpox virus recombinants expressing the harmless variant E7GGG of the HPV-16 E7 oncoprotein (DNA(E7GGG) and FP(E7GGG)) were generated. Two immunization regimens were tested in a pre-clinical mouse model by homologous (FP/FP) or heterologous (DNA/FP) prime-boost protocols to evaluate the immune response and therapeutic efficacy of the proposed HPV-16 vaccine. Low levels of anti-E7-specific antibodies were elicited after immunization, and in vivo experiments resulted in a higher number of tumor-free mice after the heterologous immunization. These results establish a preliminary indication for therapy of HPV-related tumors by the combined use of DNA and avipox recombinants, which might represent safer immunogens than vaccinia-based vaccines. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. HPV-16 E7 expression up-regulates phospholipase D activity and promotes rapamycin resistance in a pRB-dependent manner.

    Science.gov (United States)

    Rabachini, Tatiana; Boccardo, Enrique; Andrade, Rubiana; Perez, Katia Regina; Nonogaki, Suely; Cuccovia, Iolanda Midea; Villa, Luisa Lina

    2018-04-27

    Human Papillomavirus (HPV) infection is the main risk factor for the development and progression of cervical cancer. HPV-16 E6 and E7 expression is essential for induction and maintenance of the transformed phenotype. These oncoproteins interfere with the function of several intracellular proteins, including those controlling the PI3K/AKT/mTOR pathway in which Phospolipase D (PLD) and Phosphatidic acid (PA) play a critical role. PLD activity was measured in primary human keratinocytes transduced with retroviruses expressing HPV-16 E6, E7 or E7 mutants. The cytostatic effect of rapamycin, a well-known mTOR inhibitor with potential clinical applications, was evaluated in monolayer and organotypic cultures. HPV-16 E7 expression in primary human keratinocytes leads to an increase in PLD expression and activity. Moreover, this activation is dependent on the ability of HPV-16 E7 to induce retinoblastoma protein (pRb) degradation. We also show that cells expressing HPV-16 E7 or silenced for pRb acquire resistance to the antiproliferative effect of rapamycin. This is the first indication that HPV oncoproteins can affect PLD activity. Since PA can interfere with the ability of rapamycin to bind mTOR, the use of combined strategies to target mTOR and PLD activity might be considered to treat HPV-related malignancies.

  13. A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.

    Directory of Open Access Journals (Sweden)

    Olivia C Demurtas

    Full Text Available The E7 protein of the Human Papillomavirus (HPV type 16, being involved in malignant cellular transformation, represents a key antigen for developing therapeutic vaccines against HPV-related lesions and cancers. Recombinant production of this vaccine antigen in an active form and in compliance with good manufacturing practices (GMP plays a crucial role for developing effective vaccines. E7-based therapeutic vaccines produced in plants have been shown to be active in tumor regression and protection in pre-clinical models. However, some drawbacks of in whole-plant vaccine production encouraged us to explore the production of the E7-based therapeutic vaccine in Chlamydomonas reinhardtii, an organism easy to grow and transform and fully amenable to GMP guidelines.An expression cassette encoding E7GGG, a mutated, attenuated form of the E7 oncoprotein, alone or as a fusion with affinity tags (His6 or FLAG, under the control of the C. reinhardtii chloroplast psbD 5' UTR and the psbA 3' UTR, was introduced into the C. reinhardtii chloroplast genome by homologous recombination. The protein was mostly soluble and reached 0.12% of total soluble proteins. Affinity purification was optimized and performed for both tagged forms. Induction of specific anti-E7 IgGs and E7-specific T-cell proliferation were detected in C57BL/6 mice vaccinated with total Chlamydomonas extract and with affinity-purified protein. High levels of tumor protection were achieved after challenge with a tumor cell line expressing the E7 protein.The C. reinhardtii chloroplast is a suitable expression system for the production of the E7GGG protein, in a soluble, immunogenic form. The production in contained and sterile conditions highlights the potential of microalgae as alternative platforms for the production of vaccines for human uses.

  14. The clinical value of HPV E6/E7 and STAT3 mRNA detection in cervical cancer screening.

    Science.gov (United States)

    Fan, Yibing; Shen, Zongji

    2018-02-11

    To explore the value of human papillomavirus (HPV) E6/E7 and signal transducer and activator of transcription 3 (STAT3) mRNA detection in the screening of cervical lesions. 192 patients with abnormal ThinPrep cytology test (TCT) results and/or high-risk HPV infection were screened to identify possible cervical lesions in cases. Diagnoses were confirmed by histopathology. Fluorescence in situ hybridization (FISH) was performed to detect and qualify the mRNAs of HPV E6/E7, STAT3, and Survivin in cervical exfoliated cells. In addition, the performance of separate and combined mRNA detection methods were compared with TCT, HR-HPV DNA schemes respectively. 1. Compared with HPVE6/E7 and STAT3 mRNA methods, Survivin mRNA assay had poor specificity (Sp), Youden index (YI) and concordance rate. 2. HPV E6/E7, STAT3, and STAT3 + HR-HPV methods had the best Sp, concordance rate and positive predictive value (PPV) for cervical lesions screening and atypical squamous cells of undetermined significance (ASCUS) triage. For screening of high grade squamous intraepithelial lesions or greater (HSILs+), no difference was observed in the Se of mRNA detection methods in comparison with that of TCT, HR-HPV and TCT + HR-HPV, whereas the false positive rate (FPR) decreased by 41.48%/55.99%/17.19% and the colposcopy referral rate reduced by about 20.00%/25.00%/11.17%. For triage of women with ASCUS, no difference was observed in the Se of mRNA detection methods as compared to that of HR-HPV (χ 2  = 1.05, P > 0.75), while the FPR decreased by 45.83%/37.50%/41.66% and the colposcopy referral rate reduced by 32.42%/22.60%/25.28%, respectively. The Se, YI, and PPV of the combined methods increased in comparison to each method alone. 3. Compared with the TCT + HR-HPV method, HPV E6/E7 + STAT3 method had perfect Sp (95.92%) and PPV (95.40%) for screening HSILs+, the FPR and colposcopy referral rate decreased by 31.06% and 22.48% respectively. 1. The expression of HPV E6/E

  15. Detection of human papillomavirus type 18 E6 and E7-specific CD4+ T-helper 1 immunity in relation to health versus disease

    NARCIS (Netherlands)

    Welters, Marij J. P.; van der Logt, Pauline; van den Eeden, Susan J. F.; Kwappenberg, Kitty M. C.; Drijfhout, Jan Wouter; Fleuren, Gert Jan; Kenter, Gemma G.; Melief, Cornelis J. M.; van der Burg, Sjoerd H.; Offringa, Rienk

    2006-01-01

    The most common high-risk human papillomavirus types, HPV16 and 18, differ markedly with respect to their interaction with the host. Clearance of HPV18 infections generally takes longer and HPV18-positive cancers have a poorer prognosis. We therefore evaluated Th1-type immunity against the E6 and E7

  16. Genetic immunization against cervical carcinoma : induction of cytotoxic T lymphocyte activity with a recombinant alphavirus vector expressing human papillomavirus type 16 E6 and E7

    NARCIS (Netherlands)

    Daemen, T; Pries, F; Bungener, L; Kraak, M; Regts, J; Wilschut, J

    infection of genital epithelial cells with human papillomavirus (HPV) types 16 and 18 is closely associated with the development of cervical carcinoma. The transforming potential of these high-risk HPVs depends on the expression of the E6 and E7 early viral gene products. Since the expression of E6

  17. Human papillomavirus E6 and E7 oncoproteins as risk factors

    Indian Academy of Sciences (India)

    Prakash

    J. Biosci. 34(1), March 2009. 1. Introduction. Human papillomavirus (HPV) is a double-stranded DNA virus that ..... contact and loss of cell polarity (Watson et al 2003; Thomas ..... Arrand JR 1995 Translation of the human papillomavirus type 16.

  18. The Minkowski sum of a zonotope and the Voronoi polytope of the root lattice E7

    International Nuclear Information System (INIS)

    Grishukhin, Vyacheslav P

    2012-01-01

    We show that the Minkowski sum P V (E 7 )+Z(U) of the Voronoi polytope P V (E 7 ) of the root lattice E 7 and the zonotope Z(U) is a 7-dimensional parallelohedron if and only if the set U consists of minimal vectors of the dual lattice E 7 * up to scalar multiplication, and U does not contain forbidden sets. The minimal vectors of E 7 are the vectors r of the classical root system E 7 . If the r 2 -norm of the roots is set equal to 2, then the scalar products of minimal vectors from the dual lattice only take the values ±1/2. A set of minimal vectors is referred to as forbidden if it consists of six vectors, and the directions of some of these vectors can be changed so as to obtain a set of six vectors with all the pairwise scalar products equal to 1/2. Bibliography: 11 titles.

  19. Human papillomavirus type 16 E7 oncoprotein causes a delay in repair of DNA damage

    International Nuclear Information System (INIS)

    Park, Jung Wook; Nickel, Kwangok P.; Torres, Alexandra D.; Lee, Denis; Lambert, Paul F.; Kimple, Randall J.

    2014-01-01

    Background and purpose: Patients with human papillomavirus related (HPV+) head and neck cancers (HNCs) demonstrate improved clinical outcomes compared to traditional HPV negative (HPV−) HNC patients. We have recently shown that HPV+ HNC cells are more sensitive to radiation than HPV− HNC cells. However, roles of HPV oncogenes in regulating the response of DNA damage repair remain unknown. Material and methods: Using immortalized normal oral epithelial cell lines, HPV+ HNC derived cell lines, and HPV16 E7-transgenic mice we assessed the repair of DNA damage using γ-H2AX foci, single and split dose clonogenic survival assays, and immunoblot. The ability of E7 to modulate expression of proteins associated with DNA repair pathways was assessed by immunoblot. Results: HPV16 E7 increased retention of γ-H2AX nuclear foci and significantly decreased sublethal DNA damage repair. While phospho-ATM, phospho-ATR, Ku70, and Ku80 expressions were not altered by E7, Rad51 was induced by E7. Correspondingly, HPV+ HNC cell lines showed retention of Rad51 after γ-radiation. Conclusions: Our findings provide further understanding as to how HPV16 E7 manipulates cellular DNA damage responses that may underlie its oncogenic potential and influence the altered sensitivity to radiation seen in HPV+ HNC as compared to HPV− HNC

  20. Attenuated Recombinant Influenza A Virus Expressing HPV16 E6 and E7 as a Novel Therapeutic Vaccine Approach.

    Directory of Open Access Journals (Sweden)

    Christoph Jindra

    Full Text Available Persistent infection with high-risk human papillomavirus (HPV types, most often HPV16 and HPV18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. Two prophylactic virus-like particle (VLPs-based vaccines, are available that protect against vaccine type-associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. We have generated recombinant live-attenuated influenza A viruses expressing the HPV16 oncogenes E6 and E7 as experimental immunotherapeutic vaccine candidates. The influenza A virus life cycle lacks DNA intermediates as important safety feature. Different serotypes were generated to ensure efficient prime and boost immunizations. The immune response to vaccination in C57BL/6 mice was characterized by peptide ELISA and IFN-γ ELISpot, demonstrating induction of cell-mediated immunity to HPV16 E6 and E7 oncoproteins. Prophylactic and therapeutic vaccine efficacy was analyzed in the murine HPV16-positive TC-1 tumor challenge model. Subcutaneous (s.c. prime and boost vaccinations of mice with recombinant influenza A serotypes H1N1 and H3N2, followed by challenge with TC-1 cells resulted in complete protection or significantly reduced tumor growth as compared to control animals. In a therapeutic setting, s.c. vaccination of mice with established TC-1 tumors decelerated tumor growth and significantly prolonged survival. Importantly, intralesional vaccine administration induced complete tumor regression in 25% of animals, and significantly reduced tumor growth in 50% of mice. These results suggest recombinant E6E7 influenza viruses as a promising new approach for the development of a therapeutic vaccine against HPV-induced disease.

  1. Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Soyeong Park

    2016-05-01

    Full Text Available Fanconi anemia (FA is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC at sites where high-risk human papillomaviruses (HPVs are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative.

  2. Human Papillomavirus Type 16 E6 and E7 Oncoproteins Act Synergistically to Cause Head and Neck Cancer in Mice

    Science.gov (United States)

    Jabbar, Sean; Strati, Katerina; Shin, Myeong Kyun; Pitot, Henry C.; Lambert, Paul F.

    2010-01-01

    High-risk human papillomaviruses (HPVs) contribute to cervical and other anogenital cancers, and they are also linked etiologically to a subset of head and neck squamous cell carcinomas (HNSCC). We previously established a model for HPV-associated HNSCC in which we treated transgenic mice expressing the papillomaviral oncoproteins with the chemical carcinogen 4-nitroquinoline-1-oxide (4-NQO). We found that the HPV-16 E7 oncoprotein was highly potent in causing HNSCC, and its dominance masked any potential oncogenic contribution of E6, a second papillomaviral oncoprotein commonly expressed in human cancers. In the current study, we shortened the duration of treatment with 4-NQO to reduce the incidence of cancers and discovered a striking synergy between E6 and E7 in causing HNSCC. Comparing the oncogenic properties of wild-type versus mutant E6 genes in this model for HNSCC uncovered a role for some but not other cellular targets of E6 previously shown to contribute to cervical cancer. PMID:20797753

  3. High incidence of HPV-associated head and neck cancers in FA deficient mice is associated with E7's induction of DNA damage through its inactivation of pocket proteins.

    Science.gov (United States)

    Park, Jung Wook; Shin, Myeong-Kyun; Pitot, Henry C; Lambert, Paul F

    2013-01-01

    Fanconi anemia (FA) patients are highly susceptible to solid tumors at multiple anatomical sites including head and neck region. A subset of head and neck cancers (HNCs) is associated with 'high-risk' HPVs, particularly HPV16. However, the correlation between HPV oncogenes and cancers in FA patients is still unclear. We previously learned that FA deficiency in mice predisposes HPV16 E7 transgenic mice to HNCs. To address HPV16 E6's oncogenic potential under FA deficiency in HNCs, we utilized HPV16 E6-transgenic mice (K14E6) and HPV16 E6/E7-bi-transgenic mice (K14E6E7) on genetic backgrounds sufficient or deficient for one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6 mice failed to develop tumor. However, E6 and fancD2-deficiency accelerated E7-driven tumor development in K14E6E7 mice. The increased tumor incidence was more correlated with E7-driven DNA damage than proliferation. We also found that deficiency of pocket proteins, pRb, p107, and p130 that are well-established targets of E7, could recapitulate E7's induction of DNA damage. Our findings support the hypothesis that E7 induces HPV-associated HNCs by promoting DNA damage through the inactivation of pocket proteins, which explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer. Our results further demonstrate the unexpected finding that FA deficiency does not predispose E6 transgenic mice to HNCs, indicating a specificity in the synergy between FA deficiency and HPV oncogenes in causing HNCs.

  4. High incidence of HPV-associated head and neck cancers in FA deficient mice is associated with E7's induction of DNA damage through its inactivation of pocket proteins.

    Directory of Open Access Journals (Sweden)

    Jung Wook Park

    Full Text Available Fanconi anemia (FA patients are highly susceptible to solid tumors at multiple anatomical sites including head and neck region. A subset of head and neck cancers (HNCs is associated with 'high-risk' HPVs, particularly HPV16. However, the correlation between HPV oncogenes and cancers in FA patients is still unclear. We previously learned that FA deficiency in mice predisposes HPV16 E7 transgenic mice to HNCs. To address HPV16 E6's oncogenic potential under FA deficiency in HNCs, we utilized HPV16 E6-transgenic mice (K14E6 and HPV16 E6/E7-bi-transgenic mice (K14E6E7 on genetic backgrounds sufficient or deficient for one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6 mice failed to develop tumor. However, E6 and fancD2-deficiency accelerated E7-driven tumor development in K14E6E7 mice. The increased tumor incidence was more correlated with E7-driven DNA damage than proliferation. We also found that deficiency of pocket proteins, pRb, p107, and p130 that are well-established targets of E7, could recapitulate E7's induction of DNA damage. Our findings support the hypothesis that E7 induces HPV-associated HNCs by promoting DNA damage through the inactivation of pocket proteins, which explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer. Our results further demonstrate the unexpected finding that FA deficiency does not predispose E6 transgenic mice to HNCs, indicating a specificity in the synergy between FA deficiency and HPV oncogenes in causing HNCs.

  5. Phase Diagram of Binary Mixture E7:TM74A Liquid Crystals

    Directory of Open Access Journals (Sweden)

    Serafin Delica

    1999-12-01

    Full Text Available Although there are many liquid crystalline materials, difficulty is often experienced in obtaining LCs that are stable and has a wide mesophase range. In this study, mixtures of two different LCs were used to formulate a technologically viable LC operating at room temperature. Nematic E7(BDH and cholesteric TM74A were mixed at different weight ratios at 10% increments. Transition temperatures were determined via Differential Scanning Calorimetry and phase identification was done using Optical Polarizing Microscopy. The phase diagram showed the existence of three different phases for the temperature range of 10-80°C. Mixtures with 0-20% E7 exhibit only the cholesteric-nematic mesophase, which could be due to the mixture's being largely TM74A and its behavior in the temperature range considered is similar to the behavior of pure TM74A. With an increase in the concentration of E7, the smectic phase of the pure cholesteric was enhanced, as seen from the increased transition to the cholesteric-nematic phase and a broader smectic range. The cholesteric-nematic to isotropic transition increased as the nematic concentration increases, following the behavior expected from LC mixtures. For mixtures that are largely nematic (more than 50% E7, the smectic phase has vanished and the cholesteric-nematic phase dominated from 30-60°C.

  6. E7(7) constraints on counterterms in N=8 supergravity

    International Nuclear Information System (INIS)

    Beisert, N.; Elvang, H.; Freedman, D.; Kiermaier, M.; Morales, A.; Stieberger, S.

    2010-01-01

    We prove by explicit computation that 6-point matrix elements of D 4 R 4 and D 6 R 4 in N=8 supergravity have non-vanishing single-soft scalar limits, and therefore these operators violate the continuous E 7(7) symmetry. The soft limits precisely match automorphism constraints. Together with previous results for R 4 , this provides a direct proof that no E 7(7) -invariant candidate counterterm exists below 7-loop order. At 7-loops, we characterize the infinite tower of independent supersymmetric operators D 4 R 6 , R 8 , φ 2 R 8 , … with n>4 fields and prove that they all violate E 7(7) symmetry. This means that the 4-graviton amplitude determines whether or not the theory is finite at 7-loop order. We show that the corresponding candidate counterterm D 8 R 4 has a non-linear supersymmetrization such that its single- and double-soft scalar limits are compatible with E 7(7) up to and including 6-points. At loop orders 7,8,9 we provide an exhaustive account of all independent candidate counterterms with up to 16,14,12 fields, respectively, together with their potential single-soft scalar limits.

  7. Production of recombinant proteins GST L1, E6 and E7 tag HPV 16 ...

    African Journals Online (AJOL)

    In the present work recombinant proteins were produced for used in LUMINEX in order to undergo serological study of Tunisian female population. HPV types 16 L1, E6 and E7 sequences fused to their 3'-end to a sequence encoding the terminal undecapeptide of the SV40 large T-antigen (tag) were isolated from plasmids ...

  8. Oct4 is required ~E7.5 for proliferation in the primitive streak.

    Directory of Open Access Journals (Sweden)

    Brian DeVeale

    2013-11-01

    Full Text Available Oct4 is a widely recognized pluripotency factor as it maintains Embryonic Stem (ES cells in a pluripotent state, and, in vivo, prevents the inner cell mass (ICM in murine embryos from differentiating into trophectoderm. However, its function in somatic tissue after this developmental stage is not well characterized. Using a tamoxifen-inducible Cre recombinase and floxed alleles of Oct4, we investigated the effect of depleting Oct4 in mouse embryos between the pre-streak and headfold stages, ~E6.0-E8.0, when Oct4 is found in dynamic patterns throughout the embryonic compartment of the mouse egg cylinder. We found that depletion of Oct4 ~E7.5 resulted in a severe phenotype, comprised of craniorachischisis, random heart tube orientation, failed turning, defective somitogenesis and posterior truncation. Unlike in ES cells, depletion of the pluripotency factors Sox2 and Oct4 after E7.0 does not phenocopy, suggesting that ~E7.5 Oct4 is required within a network that is altered relative to the pluripotency network. Oct4 is not required in extraembryonic tissue for these processes, but is required to maintain cell viability in the embryo and normal proliferation within the primitive streak. Impaired expansion of the primitive streak occurs coincident with Oct4 depletion ∼E7.5 and precedes deficient convergent extension which contributes to several aspects of the phenotype.

  9. Molecular mobility of nematic E7 confined to molecular sieves with a low filling degree.

    Science.gov (United States)

    Brás, A R; Frunza, S; Guerreiro, L; Fonseca, I M; Corma, A; Frunza, L; Dionísio, M; Schönhals, A

    2010-06-14

    The nematic liquid crystalline mixture E7 was confined with similar filling degrees to molecular sieves with constant composition but different pore diameters (from 2.8 to 6.8 nm). Fourier transform infrared analysis proved that the E7 molecules interact via the cyanogroup with the pore walls of the molecular sieves. The molecular dynamics of the system was investigated by broadband dielectric spectroscopy (10(-2)-10(9) Hz) covering a wide temperature range of approximately 200 K from temperatures well above the isotropic-nematic transition down to the glass transition of bulk E7. A variety of relaxation processes is observed including two modes that are located close to the bulk behavior in its temperature dependence. For all confined samples, two relaxation processes, at frequencies lower than the processes observed for the bulk, were detected. At lower temperatures, their relaxation rates have different temperature dependencies whereas at higher temperatures, they seem to collapse into one chart. The temperature dependence of the slowest process (S-process) obeys the Vogel-Fulcher-Tammann law indicating a glassy dynamics of the E7 molecules anchored to the pore surface. The pore size dependence of both the Vogel temperature and fragility revealed a steplike transition around 4 nm pore size, which indicates a transition from a strong to a fragile behavior. The process with a relaxation rate in between the bulklike and the S-process (I-process) shows no dependence on the pore size. The agreement of the I-process with the behavior of a 5CB surface layer adsorbed on nonporous silica leads to the assignment of E7 molecules anchored at the outer surface of the microcrystals of the molecular sieves.

  10. Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice

    Science.gov (United States)

    Park, Soyeong; Park, Jung Wook; Pitot, Henry C.

    2016-01-01

    ABSTRACT   Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative. Importance   Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an

  11. Production of neutral heavy leptons by neutrinos in the E7 gauge model of weak interactions

    International Nuclear Information System (INIS)

    Bottino, A.; Kim, C.W.

    1977-11-01

    An attempt, is made, in the framework of the Guersey-Sikivie gauge model of weak interactions based on the E7 group, to explain the recently observed neutrino-production of a relatively long-lived neutral heavy lepton in SKAT bubble chamber experiment. It is shown that a lepton assignment with mixings among neutral leptons can explain the SKAT event. This lepton assignment is also shown to be consistent with other well-known experiments

  12. Alga-based HPV16 E7 vaccine elicits specific immune response in mice

    Czech Academy of Sciences Publication Activity Database

    Vlasák, Josef; Bříza, Jindřich; Ryba, Š.; Ludvíková, V.

    2013-01-01

    Roč. 34, č. 1 (2013), s. 141-148 ISSN 2249-7412 R&D Projects: GA AV ČR IAA500960903 Institutional support: RVO:60077344 Keywords : Chlamydomonas reinhardtii * chloroplast transformation * human papillomaviruses * E7 oncogene Subject RIV: EB - Genetics ; Molecular Biology http://pelagiaresearchlibrary.com/asian-journal-of-plant-science/vol3-iss1/AJPSR-2013-3-1-141-148.pdf

  13. Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes

    Directory of Open Access Journals (Sweden)

    Arnouk Hilal

    2009-08-01

    Full Text Available Abstract Background Infection with high-risk type human papilloma viruses (HPVs is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features. Results Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE. The median within-group coefficient of variation was 19–21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23% of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2% were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1; and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27. Conclusion This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.

  14. E7 type modular invariant Wess-Zumino theory and Gepner's string compactification

    International Nuclear Information System (INIS)

    Kato, Akishi; Kitazawa, Yoshihisa

    1989-01-01

    The report addresses the development of a general procedure to study the structure of operator algebra in off-diagonal modular invariant theories. An effort is made to carry out this procedure in E 7 type modular invariant Wess-Zumino-Witten theory and explicitly check the closure of operator product algebra, which is required for any consistent conformal field theory. The conformal field theory is utilized to construct perturbative vacuum in string theory. Apparently quite nontrivial vacuums can be constructed out of minimal models of the N = 2 superconformal theory. Here, an investigation made of the Yukawa couplings of such a model which uses E 7 type off-diagonal modular invariance. Phenomenological properties of this model is also discussed. Although off-diagonal modular invariant theories are rather special, realistic models seem to require very special manifolds. Therefore they may enhance the viability of string theory to describe real world. A study is also made on Verlinde's fusion algebra in E 7 modular invariant theory. It is determined in the holomorphic sector only. Furthermore the indicator is given by the modular transformation matrix. A pair of operators which operate on the characters play a crucial role in this theory. (Nogami, K.)

  15. Modulation of DNA methylation by human papillomavirus E6 and E7 oncoproteins in cervical cancer

    Science.gov (United States)

    Sen, Prakriti; Ganguly, Pooja; Ganguly, Niladri

    2018-01-01

    Human papillomaviruses (HPVs) are double stranded circular DNA viruses that infect cutaneous and mucosal epithelial cells. Almost 99% of cervical cancer has a HPV infection. The early oncoproteins E6 and E7 are important in this cellular transformation process. Epigenetic mechanisms have long been known to result in decisive alterations in DNA, leading to alterations in DNA-protein interactions, alterations in chromatin structure and compaction and significant alterations in gene expression. The enzymes responsible for these epigenetic modifications are DNA methyl transferases (DNMTs), histone acetylases and deacetylases. Epigenetics has an important role in cancer development by modifying the cellular micro environment. In this review, the authors discuss the role of HPV oncoproteins E6 and E7 in modulating the epigenetic mechanisms inside the host cell. The oncoproteins induce the expression of DNMTs which lead to aberrant DNA methylations and disruption of the normal epigenetic processes. The E7 oncoprotein may additionally directly bind and induce methyl transferase activity of the enzyme. These modulations lead to altered gene expression levels, particularly the genes involved in apoptosis, cell cycle and cell adhesion. In addition, the present review discusses how epigenetic mechanisms may be targeted for possible therapeutic interventions for HPV mediated cervical cancer. PMID:29285184

  16. Tyrosine B10 triggers a heme propionate hydrogen bonding network loop with glutamine E7 moiety

    International Nuclear Information System (INIS)

    Ramos-Santana, Brenda J.; López-Garriga, Juan

    2012-01-01

    Highlights: ► H-bonding network loop by PheB10Tyr mutation is proposed. ► The propionate group H-bonding network restricted the flexibility of the heme. ► The hydrogen bonding interaction modulates the electron density of the iron. ► Propionate H-bonding network loop explains the heme-ligand stabilization. -- Abstract: Propionates, as peripheral groups of the heme active center in hemeproteins have been described to contribute in the modulation of heme reactivity and ligand selection. These electronic characteristics prompted the question of whether the presence of hydrogen bonding networks between propionates and distal amino acids present in the heme ligand moiety can modulate physiological relevant events, like ligand binding association and dissociation activities. Here, the role of these networks was evaluated by NMR spectroscopy using the hemoglobin I PheB10Tyr mutant from Lucina pectinata as model for TyrB10 and GlnE7 hemeproteins. 1 H-NMR results for the rHbICN PheB10Tyr derivative showed chemical shifts of TyrB10 OHη at 31.00 ppm, GlnE7 N ε1 H/N ε2 H at 10.66 ppm/−3.27 ppm, and PheE11 C δ H at 11.75 ppm, indicating the presence of a crowded, collapsed, and constrained distal pocket. Strong dipolar contacts and inter-residues crosspeaks between GlnE7/6-propionate group, GlnE7/TyrB10 and TyrB10/CN suggest that this hydrogen bonding network loop between GlnE7, TyrB10, 6-propionate group, and the heme ligand contribute significantly to the modulation of the heme iron electron density as well as the ligand stabilization mechanism. Therefore, the network loop presented here support the fact that the electron withdrawing character of the hydrogen bonding is controlled by the interaction of the propionates and the nearby electronic environments contributing to the modulation of the heme electron density state. Thus, we hypothesize that in hemeproteins with similar electrostatic environment the flexibility of the heme-6-propionate promotes a hydrogen

  17. Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears.

    Science.gov (United States)

    Ren, Chenchen; Zhu, Yuanhang; Yang, Li; Zhang, Xiaoan; Liu, Ling; Ren, Chunying

    2018-02-01

    The aim of this study was to investigate the clinical performance of high risk (HR) HPV E6/E7 mRNA assay in detecting cervical high-grade intraepithelial neoplasia and cancer among women with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou (Pap) smears. A total of 160 patients with ASCUS who underwent HR-HPV DNA assay, HR-HPV E6/E7 mRNA assay and colposcopy biopsy at Third Affiliated Hospital of Zhengzhou University, China, from December 2015 to March 2017, were enrolled. Logistic regression analysis was used to evaluate the relationship between pathological results with clinical biologic factors. Univariate analysis showed that the qualitative results of HR-HPV DNA, qualitative results of HR-HPV E6/E7 mRNA and expression levels of HR-HPV E6/E7 mRNA were risk factors of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (all P HPV E6/E7 mRNA was associated with high-grade CIN and cervical cancer (OR = 8.971, 95% CI = 2.572-31.289, P = 0.001). An optimal cut-off value of ≥ 558.26 copies/ml was determined using receiver operating characteristic curve, and specificity of cut-off value were higher than E6/E7 mRNA qualitative assay and DNA qualitative assay. HPV E6/E7 mRNA quantitative assay may be a valuable tool in triage of ASCUS pap smears. A high specificity of E6/E7 mRNA quantitative assay as a triage test in women with ASCUS can be translated into a low referral for colposcopy.

  18. A prospective study of women with ASCUS or LSIL pap smears at baseline and HPV E6/E7 mRNA positive: a 3-year follow-up.

    Science.gov (United States)

    Bruno, M T; Ferrara, M; Fava, V; Barrasso, G; Panella, M M

    2018-04-01

    Human papillomavirus (HPV) testing is used in the triage of women with a borderline smear result. The efficiency of testing women with a low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells of undetermined significance (ASCUS) is less clear. For this reason we used a new HPV test that detects E6/E7 messenger RNA (mRNA), which might have a higher specificity. The objective of this prospective study was to assess whether HPV E6/E7 mRNA positivity in women with ASCUS and LSIL at baseline, is able to predict those women who have a high risk of developing a histological cervical intraepithelial neoplasia (CIN2) or worse lesion. We took into consideration the women's age and HPV DNA genotype and followed them up for 3 years. Cervical samples from women with high-risk HPV (HR-HPV) DNA-positive ASCUS (n = 90) or LSIL (n = 222) were tested for the presence of HR-HPV E6/E7 mRNA and the women were monitored for the development of histopathologically verified CIN2+. Thirteen patients with ASCUS and 17 with LSIL did not complete follow-up. All patients with LSIL and ASCUS, enrolled in this study, had confirmed lesions at the colposcopic examination. Follow-up was available for 312 women, 193 were positive in the HR-HPV DNA test and 93 had a HPV E6/E7 mRNA positive test. Finally, 22 women positive in the HPV DNA test for high-risk genotypes and with positive E6/E7 mRNA had a histologically confirmed CIN2+. Only two cases with negative HPV E6/E7 mRNA had CIN2+. The study shows that women positive in the HPV E6/E7 mRNA test have a greater risk of malignant progression of cervical lesions and therefore deserve greater attention and earlier check-ups.

  19. Immunization with mutant HPV16 E7 protein inhibits the growth of TC-1 cells in tumor-bearing mice.

    Science.gov (United States)

    Li, Yan-Li; Ma, Zhong-Liang; Zhao, Yue; Zhang, Jing

    2015-04-01

    Two human papillomavirus (HPV) 16 oncogenic proteins, E6 and E7, are co-expressed in the majority of HPV16-induced cervical cancer cells. Thus, the E6 and E7 proteins are good targets for developing therapeutic vaccines for cervical cancer. In the present study, immunization with the mutant non-transforming HPV16 E7 (mE7) protein was demonstrated to inhibit the growth of TC-1 cells in the TC-1 mouse model. The HPV16 mE7 gene was amplified by splicing overlap extension polymerase chain reaction using pET-28a(+)-E7 as a template, and the gene was cloned into pET-28a(+) to form pET-28a(+)-mE7. Compared with the E7 protein, mE7 lacks amino acid residues 94-98, and at residue 24, there is a Cys to Gly substitution. pET-28a(+)-mE7 was then introduced into Escherichia coli Rosetta. The expression of mE7 was induced by isopropyl β-D-1-thiogalactopyranoside. The mE7 protein was purified using Ni-NTA agarose and detected by SDS-PAGE and western blot analysis. In the tumor prevention model, no tumor was detected in the mice vaccinated with the mE7 protein. After 40 days, the tumor-free mice and control mice were challenged with 2×10 5 TC-1 cells. All control mice developed tumors six days later, but mE7 immunized mice were tumor free until 90 days. In the tumor therapy model, the TC-1 cells were initially injected subcutaneously, and the mice were subsequently vaccinated. Vaccination against the mE7 protein may significantly inhibit TC-1 cell growth compared to the control. These results demonstrated that immunization with the HPV16 mE7 protein elicited a long-term protective immunity against TC-1 tumor growth and generated a significant inhibition of TC-1 growth in a TC-1 mouse model.

  20. Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers

    OpenAIRE

    Chang, J T-C; Kuo, T-F; Chen, Y-J; Chiu, C-C; Lu, Y-C; Li, H-F; Shen, C-R; Cheng, A-J

    2010-01-01

    Infection with high-risk types (type 16 or type 18) of human papillomaviruses (HPVs) increases a patient's risk of cervical cancer. Given the importance of the cervix and the severe side effects resulting from traditional cancer therapies, this study aimed to achieve targeted inhibition of viral oncogenes in tumor cells using small interfering RNAs (siRNA). To accomplish this, we developed nine siRNAs against either the E6 or E7 genes of HPV-16 or HPV-18 in several combinations, yielding siRN...

  1. ANTIBODIES TO HUMAN PAPILLOMAVIRUS TYPE-16 E7 RELATED TO CLINICOPATHOLOGICAL DATA IN PATIENTS WITH CERVICAL-CARCINOMA

    NARCIS (Netherlands)

    BAAY, MFD; DUK, JM; BURGER, MPM; WALBOOMERS, J; TERSCHEGGET, J; GROENIER, KH; DEBRUIJN, HWA; STOLZ, E; HERBRINK, P

    Aims-To investigate the correlation between antibodies to the transforming protein E7 of human papillomavirus (HPV) type 16 and clinicopathological indices in women with cervical squamous carcinoma. Methods-A synthetic peptide of the HPV type 16 E7 protein (amino acids 6 to 35) was used to screen

  2. Single-tube multiplex PCR using type-specific E6/E7 primers and capillary electrophoresis genotypes 21 human papillomaviruses in neoplasia

    Directory of Open Access Journals (Sweden)

    Warenholt Janina

    2011-01-01

    Full Text Available Abstract Background Human papillomavirus (HPV E6/E7 type-specific oncogenes are required for cervical carcinogenesis. Current PCR protocols for genotyping high-risk HPV in cervical screening are not standardized and usually use consensus primers targeting HPV capsid genes, which are often deleted in neoplasia. PCR fragments are detected using specialized equipment and extra steps, including probe hybridization or primer extension. In published papers, analytical sensitivity is typically compared with a different protocol on the same sample set. A single-tube multiplex PCR containing type-specific primers was developed to target the E6/E7 genes of two low-risk and 19 high-risk genotypes (HPV6, 11 and 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82 and the resulting short fragments were directly genotyped by high-resolution fluorescence capillary electrophoresis. Results The method was validated using long oligonucleotide templates, plasmid clones and 207 clinical samples of DNA from liquid-based cytology, fresh and formalin-fixed specimens and FTA Microcards® imprinted with cut tumor surfaces, swabbed cervical cancers or ejected aspirates from nodal metastases of head and neck carcinomas. Between one and five long oligonucleotide targets per sample were detected without false calls. Each of the 21 genotypes was detected in the clinical sample set with up to five types simultaneously detected in individual specimens. All 101 significant cervical neoplasias (CIN 2 and above, except one adenocarcinoma, contained E6/E7 genes. The resulting genotype distribution accorded with the national pattern with HPV16 and 18 accounting for 69% of tumors. Rare HPV types 70 and 73 were present as the sole genotype in one carcinoma each. One cervical SCC contained DNA from HPV6 and 11 only. Six of twelve oropharyngeal cancer metastases and three neck metastases of unknown origin bore E6/E7 DNA; all but one were HPV16. One neck

  3. Human papillomavirus type 16 E7 oncoprotein engages but does not abrogate the mitotic spindle assembly checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yueyang [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States); Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States)

    2012-10-10

    The mitotic spindle assembly checkpoint (SAC) ensures faithful chromosome segregation during mitosis by censoring kinetochore-microtubule interactions. It is frequently rendered dysfunctional during carcinogenesis causing chromosome missegregation and genomic instability. There are conflicting reports whether the HPV16 E7 oncoprotein drives chromosomal instability by abolishing the SAC. Here we report that degradation of mitotic cyclins is impaired in cells with HPV16 E7 expression. RNAi-mediated depletion of Mad2 or BubR1 indicated the involvement of the SAC, suggesting that HPV16 E7 expression causes sustained SAC engagement. Mutational analyses revealed that HPV16 E7 sequences that are necessary for retinoblastoma tumor suppressor protein binding as well as sequences previously implicated in binding the nuclear and mitotic apparatus (NuMA) protein and in delocalizing dynein from the mitotic spindle contribute to SAC engagement. Importantly, however, HPV16 E7 does not markedly compromise the SAC response to microtubule poisons.

  4. Differential gene expression between skin and cervix induced by the E7 oncoprotein in a transgenic mouse model

    Science.gov (United States)

    Ibarra Sierra, E; Díaz Chávez, J; Cortés-Malagón, EM; Uribe-Figueroa, L; Hidalgo-Miranda, A; Lambert, PF; Gariglio, P

    2013-01-01

    HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17β-estradiol. In untreated mice, E7 also induces skin tumors late in life albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes including signal transduction, transport, metabolic process, cell adhesion, apoptosis, cell differentiation, immune response and inflammatory response. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia including DMBT1, GLI1 and 17βHSD2 in cervix, as well as MMP2, 12, 14, 19 and 27 in skin. PMID:22980503

  5. Recurrent respiratory papillomatosis: a longitudinal study comparing severity associated with human papilloma viral types 6 and 11 and other risk factors in a large pediatric population.

    Science.gov (United States)

    Wiatrak, Brian J; Wiatrak, Deborah W; Broker, Thomas R; Lewis, Linda

    2004-11-01

    A database was developed for prospective, longitudinal study of recurrent respiratory papillomatosis (RRP) in a large population of pediatric patients. Data recorded for each patient included epidemiological factors, human papilloma virus (HPV) type, clinical course, staged severity of disease at each surgical intervention, and frequency of surgical intervention. The study hypothesizes that patients with HPV type 11 (HPV-11) and patients younger than 3 years of age at diagnosis are at risk for more aggressive and extensive disease. The 10-year prospective epidemiological study used disease staging for each patient with an original scoring system. Severity scores were updated at each surgical procedure. Parents of children with RRP referred to the authors' hospital completed a detailed epidemiological questionnaire at the initial visit or at the first return visit after the study began. At the first endoscopic debridement after study enrollment, tissue was obtained and submitted for HPV typing using polymerase chain reaction techniques and in situ hybridization. Staging of disease severity was performed in real time at each endoscopic procedure using an RRP scoring system developed by one of the authors (B.J.W.). The frequency of endoscopic operative debridement was recorded for each patient. Information in the database was analyzed to identify statistically significant relationships between extent of disease and/or HPV type, patient age at diagnosis, and selected epidemiological factors. The study may represent the first longitudinal prospective analysis of a large pediatric RRP population. Fifty-eight of the 73 patients in the study underwent HPV typing. Patients infected with HPV-11 were significantly more likely to have higher severity scores, require more frequent surgical intervention, and require adjuvant therapy to control disease progression. In addition, patients with HPV-11 RRP were significantly more likely to develop tracheal disease, to require

  6. Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

    Science.gov (United States)

    Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

    2011-01-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future. PMID:21865393

  7. Evidence for alteration of EZH2, BMI1, and KDM6A and epigenetic reprogramming in human papillomavirus type 16 E6/E7-expressing keratinocytes.

    Science.gov (United States)

    Hyland, Paula L; McDade, Simon S; McCloskey, Rachel; Dickson, Glenda J; Arthur, Ken; McCance, Dennis J; Patel, Daksha

    2011-11-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.

  8. Antitumor properties of (5E,7E) analogs of vitamin D3.

    Science.gov (United States)

    Filip, B; Milczarek, M; Wietrzyk, J; Chodyński, M; Kutner, A

    2010-07-01

    Geometric isomers (5E,7E) of major active metabolites of vitamin D3 [1alpha,25(OH)2D3 and (24R)-1,24(OH)2D3] were synthesized by a new convenient procedure. Vitamin D triene system of the metabolites was first derivatized as a Diels-Alder adduct. Removal of the triene protecting group, in a key synthetic step, yielded the title compounds PRI-2208 and PRI-2209, respectively. The analogs were examined for their antiproliferative activity in vitro against human breast cancer cells (MCF-7) and promyelocytic leukemia (HL-60) cells. The activity was compared with one of the parent compounds. Both analogs examined revealed similar or higher antiproliferative activity compared to 1alpha,25(OH)2D3 or to (24R)-1,24(OH)2D3. The studies of calcemic activity in vivo showed that analogs PRI-2208 and PRI-2209 did not influence the serum calcium level in doses, in which 1alpha,25(OH)2D3 or (24R)-1,24(OH)2D3 significantly increased this level. The antitumor activity of these analogs in the LLC mice tumor model was studied. Analog PRI-2208 was found to be more active in inhibiting LLC tumor growth than 1alpha,25(OH)2D3, as well as than PRI-2191 and PRI-2209. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  9. Suppression of HPV E6 and E7 expression by BAF53 depletion in cervical cancer cells

    International Nuclear Information System (INIS)

    Lee, Kiwon; Lee, Ah-Young; Kwon, Yunhee Kim; Kwon, Hyockman

    2011-01-01

    Highlights: → Integration of HPV into host genome critical for activation of E6 and E7 oncogenes. → BAF53 is essential for higher-order chromatin structure. → BAF53 knockdown suppresses E6 and E7 from HPV integrants, but not from episomal HPVs. → BAF53 knockdown decreases H3K9Ac and H4K12Ac on P105 promoter of integrated HPV 18. → BAF53 knockdown restores the p53-dependent signaling pathway in HeLa and SiHa cells. -- Abstract: Deregulation of the expression of human papillomavirus (HPV) oncogenes E6 and E7 plays a pivotal role in cervical carcinogenesis because the E6 and E7 proteins neutralize p53 and Rb tumor suppressor pathways, respectively. In approximately 90% of all cervical carcinomas, HPVs are found to be integrated into the host genome. Following integration, the core-enhancer element and P105 promoter that control expression of E6 and E7 adopt a chromatin structure that is different from that of episomal HPV, and this has been proposed to contribute to activation of E6 and E7 expression. However, the molecular basis underlying this chromatin structural change remains unknown. Previously, BAF53 has been shown to be essential for the integrity of higher-order chromatin structure and interchromosomal interactions. Here, we examined whether BAF53 is required for activated expression of E6 and E7 genes. We found that BAF53 knockdown led to suppression of expression of E6 and E7 genes from HPV integrants in cervical carcinoma cell lines HeLa and SiHa. Conversely, expression of transiently transfected HPV18-LCR-Luciferase was not suppressed by BAF53 knockdown. The level of the active histone marks H3K9Ac and H4K12Ac on the P105 promoter of integrated HPV 18 was decreased in BAF53 knockdown cells. BAF53 knockdown restored the p53-dependent signaling pathway in HeLa and SiHa cells. These results suggest that activated expression of the E6 and E7 genes of integrated HPV is dependent on BAF53-dependent higher-order chromatin structure or nuclear motor

  10. Recombinant Kunjin virus replicon vaccines induce protective T-cell immunity against human papillomavirus 16 E7-expressing tumour

    International Nuclear Information System (INIS)

    Herd, Karen A.; Harvey, Tracey; Khromykh, Alexander A.; Tindle, Robert W.

    2004-01-01

    The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses

  11. Synthesis of E7 peptide-modified biodegradable polyester with the improving affinity to mesenchymal stem cells

    International Nuclear Information System (INIS)

    Li, Qian; Xing, Dongming; Ma, Lie; Gao, Changyou

    2017-01-01

    As the most promising stem cell, bone marrow-derived mesenchymal stem cells (BMSCs) has attracted many attentions and applied widely in regenerative medicine. A biodegradable polyester with tunable affinity to BMSCs plays critical role in determining the properties of the BMSCs-based constructs. In this study, maleimide functionalized biodegradable polyester (P(MTMC-LA)) was synthesized through ring-opening copolymerization between L-lactide (LA) and furan-maleimide functionalized trimethylene carbonate (FMTMC) and a subsequent retro Diels-Alder reaction. P(MTMC-LA) was modified by different amounts of BMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry to investigate the effect on BMSCs. The E7 peptide modified P(MTMC-LA) was casted into films on glass slides and BMSCs were seeded onto the films. In vitro study showed that E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation compared to unmodified P(MTMC-LA) film. Besides, the adhesion and proliferation were enhanced by the increasing peptide grafting ratio. These results indicated that the novel biodegradable polyester can serve as a biomaterial with great potential application in tissue engineering and regenerative medicine. - Highlights: • P(MTMC-LA) was synthesized through ring-opening copolymerization and retro Diels-Alder reaction. • P(MTMC-LA) was modified by dBMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry. • E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation.

  12. Synthesis of E7 peptide-modified biodegradable polyester with the improving affinity to mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qian; Xing, Dongming; Ma, Lie, E-mail: liema@zju.edu.cn; Gao, Changyou

    2017-04-01

    As the most promising stem cell, bone marrow-derived mesenchymal stem cells (BMSCs) has attracted many attentions and applied widely in regenerative medicine. A biodegradable polyester with tunable affinity to BMSCs plays critical role in determining the properties of the BMSCs-based constructs. In this study, maleimide functionalized biodegradable polyester (P(MTMC-LA)) was synthesized through ring-opening copolymerization between L-lactide (LA) and furan-maleimide functionalized trimethylene carbonate (FMTMC) and a subsequent retro Diels-Alder reaction. P(MTMC-LA) was modified by different amounts of BMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry to investigate the effect on BMSCs. The E7 peptide modified P(MTMC-LA) was casted into films on glass slides and BMSCs were seeded onto the films. In vitro study showed that E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation compared to unmodified P(MTMC-LA) film. Besides, the adhesion and proliferation were enhanced by the increasing peptide grafting ratio. These results indicated that the novel biodegradable polyester can serve as a biomaterial with great potential application in tissue engineering and regenerative medicine. - Highlights: • P(MTMC-LA) was synthesized through ring-opening copolymerization and retro Diels-Alder reaction. • P(MTMC-LA) was modified by dBMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry. • E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation.

  13. In situ hybridization detection methods for HPV16 E6/E7 mRNA in identifying transcriptionally active HPV infection of oropharyngeal carcinoma: an updating.

    Science.gov (United States)

    Volpi, Chiara C; Ciniselli, Chiara M; Gualeni, Ambra V; Plebani, Maddalena; Alfieri, Salvatore; Verderio, Paolo; Locati, Laura; Perrone, Federica; Quattrone, Pasquale; Carbone, Antonino; Pilotti, Silvana; Gloghini, Annunziata

    2018-04-01

    The aim of this study is to compare 2 in situ hybridization (ISH) detection methods for human papilloma virus (HPV) 16 E6/E7 mRNA, that is, the RNAscope 2.0 High Definition (HD) and the upgraded RNAscope 2.5 HD version. The RNAscope 2.5 HD has recently replaced the RNAscope 2.0 HD detection kit. Therefore, this investigation starts from the need to analytically validate the new mRNA ISH assay and, possibly, to refine the current algorithm for HPV detection in oropharyngeal squamous cell carcinoma with the final goal of applying it to daily laboratory practice. The study was based on HPV status and on generated data, interpreted by a scoring algorithm. The results highlighted that the compared RNAscope HPV tests had a good level of interchangeability and enabled to identify oropharyngeal squamous cell carcinoma that are truly driven by high-risk HPV infection. This was also supported by the comparison of the RNAscope HPV test with HPV E6/E7 mRNA real-time reverse-transcription polymerase chain reaction in a fraction of cases where material for HPV E6/E7 mRNA real-time reverse-transcription polymerase chain reaction was available. Furthermore, the algorithm that associates p16 immunohistochemistry with the identification of HPV mRNA by RNAscope was more effective than the one that associated p16 immunohistochemistry with the identification of HPV DNA by ISH. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Recurrent respiratory papillomatosis: HPV genotypes and risk of high-grade laryngeal neoplasia.

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    Turid Omland

    Full Text Available Patients with recurrent respiratory papillomatosis (RRP in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma. High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR = 2.35, 95% CI 1.1, 4.99, as well as respiratory tract carcinomas (RR = 48, 95% CI 10.72, 214.91. In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract.

  15. Asociación entre la presencia de anticuerpos anti-Ras y anti-VPH16 E4/E7 y lesiones intraepiteliales del cérvix Association between anti-Ras and anti-HPV16 E4/E7 antibodies with cervical intraepithelial lesions

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    Sara Vázquez-Corzo

    2003-10-01

    cervical lesion showed that: a the presence of antibodies against two proteins predicts the presence of CIN I-II lesions, and b the presence of three antibodies predicts a CIN III lesion. CONCLUSIONS: The presence of serum antibodies against E4, E7 and Ras, together with other diagnostic techniques, could be useful for the timely detection of early uterine cervical lesions associated to HPV in women at risk of developing cancer.

  16. Antitumor HPV E7-specific CTL activity elicited by in vivo engineered exosomes produced through DNA inoculation

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    Di Bonito P

    2017-06-01

    Full Text Available Paola Di Bonito,1 Chiara Chiozzini,2 Claudia Arenaccio,2 Simona Anticoli,2 Francesco Manfredi,2 Eleonora Olivetta,2 Flavia Ferrantelli,2 Emiliana Falcone,3 Anna Ruggieri,3 Maurizio Federico2 1Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy; 2National AIDS Center, Istituto Superiore di Sanità, Rome, Italy; 3Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy Abstract: We recently proved that exosomes engineered in vitro to deliver high amounts of HPV E7 upon fusion with the Nefmut exosome-anchoring protein elicit an efficient anti-E7 cytotoxic T lymphocyte immune response. However, in view of a potential clinic application of this finding, our exosome-based immunization strategy was faced with possible technical difficulties including industrial manufacturing, cost of production, and storage. To overcome these hurdles, we designed an as yet unproven exosome-based immunization strategy relying on delivery by intramuscular inoculation of a DNA vector expressing Nefmut fused with HPV E7. In this way, we predicted that the expression of the Nefmut/E7 vector in muscle cells would result in a continuous source of endogenous (ie, produced by the inoculated host engineered exosomes able to induce an E7-specific immune response. To assess this hypothesis, we first demonstrated that the injection of a Nefmut/green fluorescent protein-expressing vector led to the release of fluorescent exosomes, as detected in plasma of inoculated mice. Then, we observed that mice inoculated intramuscularly with a vector expressing Nefmut/E7 developed a CD8+ T-cell immune response against both Nef and E7. Conversely, no CD8+ T-cell responses were detected upon injection of vectors expressing either the wild-type Nef isoform of E7 alone, most likely a consequence of their inefficient exosome incorporation. The production of immunogenic exosomes in the DNA

  17. Prognostic value of HPV E6/E7 mRNA assay in women with negative colposcopy or CIN1 histology result: a follow-up study.

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    Paolo Giorgi Rossi

    Full Text Available Pap test, and especially HPV DNA test, identify a large group of women who do not have any clinically relevant lesions, i.e., CIN2+ (Cervical Intraepithelial Neoplasia grade 2 or worse, but who are at greater risk of getting lesions in the future. The follow up of these women needs new biomarkers with prognostic value. The objective of this study is to evaluate the prognostic value of E6/E7 mRNA over-expression assay (PreTect HPV-Proofer, Norchip for 5 HR-HPV types (16, 18, 31, 33, and 45 for progression to CIN2+ after a negative colposcopy. This prospective study, conducted at four Italian centres, enrolled 673 women with either a negative colposcopy or a negative or CIN1 histology. The clinical end-point was histological confirmation of CIN2+. Women were classified at baseline according to mRNA results and managed according to local colposcopy protocols. At least one conclusive follow-up test was obtained for 347 women (25 months average lapse since recruitment, range 5-74. Only seven CIN2+ were detected during follow up, three among the 82 women positive for mRNA at baseline, two among the 250 negative (Fisher exact test, p = 0.02, and two among the 12 with an invalid test. Absolute CIN2+ risk was 6.7/1,000 person/years in the whole cohort. The absolute CIN2+ risk was 18.4/1,000 person/years and 3.6/1,000 person/years in mRNA-positive and mRNA-negative women, respectively. In conclusion, E6/E7 mRNA over-expression appears to be a good candidate as a prognostic biomarker to manage HR-HPV DNA-positive women with negative colposcopy or histology, particularly in order to decrease follow-up intensity in those who are negative.

  18. Langerhans cell homeostasis and activation is altered in hyperplastic human papillomavirus type 16 E7 expressing epidermis.

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    Nor Malia Abd Warif

    Full Text Available It has previously been shown that expression of human papillomavirus type 16 (HPV E7 in epidermis causes hyperplasia and chronic inflammation, characteristics of pre-malignant lesions. Importantly, E7-expressing epidermis is strongly immune suppressed and is not rejected when transplanted onto immune competent mice. Professional antigen presenting cells are considered essential for initiation of the adaptive immune response that results in graft rejection. Langerhans cells (LC are the only antigen presenting cells located in normal epidermis and altered phenotype and function of these cells may contribute to the immune suppressive microenvironment. Here, we show that LC are atypically activated as a direct result of E7 expression in the epidermis, and independent of the presence of lymphocytes. The number of LC was significantly increased and the LC are functionally impaired, both in migration and in antigen uptake. However when the LC were extracted from K14E7 skin and matured in vitro they were functionally competent to present and cross-present antigen, and to activate T cells. The ability of the LC to present and cross-present antigen following maturation supports retention of full functional capacity when removed from the hyperplastic skin microenvironment. As such, opportunities are afforded for the development of therapies to restore normal LC function in hyperplastic skin.

  19. HPV16-E7 expression in squamous epithelium creates a local immune suppressive environment via CCL2- and CCL5- mediated recruitment of mast cells.

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    Anne-Sophie Bergot

    2014-10-01

    Full Text Available Human Papillomavirus (HPV 16 E7 protein promotes the transformation of HPV infected epithelium to malignancy. Here, we use a murine model in which the E7 protein of HPV16 is expressed as a transgene in epithelium to show that mast cells are recruited to the basal layer of E7-expressing epithelium, and that this recruitment is dependent on the epithelial hyperproliferation induced by E7 by inactivating Rb dependent cell cycle regulation. E7 induced epithelial hyperplasia is associated with increased epidermal secretion of CCL2 and CCL5 chemokines, which attract mast cells to the skin. Mast cells in E7 transgenic skin, in contrast to those in non-transgenic skin, exhibit degranulation. Notably, we found that resident mast cells in E7 transgenic skin cause local immune suppression as evidenced by tolerance of E7 transgenic skin grafts when mast cells are present compared to the rejection of mast cell-deficient E7 grafts in otherwise competent hosts. Thus, our findings suggest that mast cells, recruited towards CCL2 and CCL5 expressed by epithelium induced to proliferate by E7, may contribute to an immunosuppressive environment that enables the persistence of HPV E7 protein induced pre-cancerous lesions.

  20. Nuclear import of cutaneous beta genus HPV8 E7 oncoprotein is mediated by hydrophobic interactions between its zinc-binding domain and FG nucleoporins

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    Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

    2014-01-20

    We have previously discovered and characterized the nuclear import pathways for the E7 oncoproteins of mucosal alpha genus HPVs, type 16 and 11. Here we investigated the nuclear import of cutaneous beta genus HPV8 E7 protein using confocal microscopy after transfections of HeLa cells with EGFP-8E7 and mutant plasmids and nuclear import assays in digitonin-permeabilized HeLa cells. We determined that HPV8 E7 contains a nuclear localization signal (NLS) within its zinc-binding domain that mediates its nuclear import. Furthermore, we discovered that a mostly hydrophobic patch {sub 65}LRLFV{sub 69} within the zinc-binding domain is essential for the nuclear import and localization of HPV8 E7 via hydrophobic interactions with the FG nucleoporins Nup62 and Nup153. Substitution of the hydrophobic residues within the {sub 65}LRLFV{sub 69} patch to alanines, and not R66A mutation, disrupt the interactions between the 8E7 zinc-binding domain and Nup62 and Nup153 and consequently inhibit nuclear import of HPV8 E7. - Highlights: • HPV8 E7 has a cNLS within its zinc-binding domain that mediates its nuclear import. • Discovery of a hydrophobic patch that is critical for the nuclear import of HPV8 E7. • HPV8 E7 nuclear import is mediated by hydrophobic interactions with FG-Nups, Nup62 and Nup153.

  1. DNA vaccines based on chimeric potyvirus-like particles carrying HPV16 E7 peptide (aa 44-60)

    Czech Academy of Sciences Publication Activity Database

    Pokorná, D.; Čeřovská, Noemi; Šmahel, M.; Moravec, Tomáš; Ludvíková, V.; Machková, J.; Synková, Helena; Dušková, M.; Hozák, P.; Velemínský, Jiří

    2005-01-01

    Roč. 14, č. 4 (2005), s. 1045-1053 ISSN 1021-335X R&D Projects: GA ČR GA310/00/0381 Grant - others:IGA MHCR NC7552-3/2003 Institutional research plan: CEZ:AV0Z50380511 Keywords : human papillomavirus * E7 * virus-like particles Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.572, year: 2005

  2. HPV-E7 Delivered by Engineered Exosomes Elicits a Protective CD8+ T Cell-Mediated Immune Response

    Science.gov (United States)

    Di Bonito, Paola; Ridolfi, Barbara; Columba-Cabezas, Sandra; Giovannelli, Andrea; Chiozzini, Chiara; Manfredi, Francesco; Anticoli, Simona; Arenaccio, Claudia; Federico, Maurizio

    2015-01-01

    We developed an innovative strategy to induce a cytotoxic T cell (CTL) immune response against protein antigens of choice. It relies on the production of exosomes, i.e., nanovesicles spontaneously released by all cell types. We engineered the upload of huge amounts of protein antigens upon fusion with an anchoring protein (i.e., HIV-1 Nefmut), which is an inactive protein incorporating in exosomes at high levels also when fused with foreign proteins. We compared the immunogenicity of engineered exosomes uploading human papillomavirus (HPV)-E7 with that of lentiviral virus-like particles (VLPs) incorporating equivalent amounts of the same antigen. These exosomes, whose limiting membrane was decorated with VSV-G, i.e., an envelope protein inducing pH-dependent endosomal fusion, proved to be as immunogenic as the cognate VLPs. It is noteworthy that the immunogenicity of the engineered exosomes remained unaltered in the absence of VSV-G. Most important, we provide evidence that the inoculation in mouse of exosomes uploading HPV-E7 induces production of anti-HPV E7 CTLs, blocks the growth of syngeneic tumor cells inoculated after immunization, and controls the development of tumor cells inoculated before the exosome challenge. These results represent the proof-of-concept about both feasibility and efficacy of the Nefmut-based exosome platform for the induction of CD8+ T cell immunity. PMID:25760140

  3. HPV-E7 Delivered by Engineered Exosomes Elicits a Protective CD8+ T Cell-Mediated Immune Response

    Directory of Open Access Journals (Sweden)

    Paola Di Bonito

    2015-03-01

    Full Text Available We developed an innovative strategy to induce a cytotoxic T cell (CTL immune response against protein antigens of choice. It relies on the production of exosomes, i.e., nanovesicles spontaneously released by all cell types. We engineered the upload of huge amounts of protein antigens upon fusion with an anchoring protein (i.e., HIV-1 Nefmut, which is an inactive protein incorporating in exosomes at high levels also when fused with foreign proteins. We compared the immunogenicity of engineered exosomes uploading human papillomavirus (HPV-E7 with that of lentiviral virus-like particles (VLPs incorporating equivalent amounts of the same antigen. These exosomes, whose limiting membrane was decorated with VSV-G, i.e., an envelope protein inducing pH-dependent endosomal fusion, proved to be as immunogenic as the cognate VLPs. It is noteworthy that the immunogenicity of the engineered exosomes remained unaltered in the absence of VSV-G. Most important, we provide evidence that the inoculation in mouse of exosomes uploading HPV-E7 induces production of anti-HPV E7 CTLs, blocks the growth of syngeneic tumor cells inoculated after immunization, and controls the development of tumor cells inoculated before the exosome challenge. These results represent the proof-of-concept about both feasibility and efficacy of the Nefmut-based exosome platform for the induction of CD8+ T cell immunity.

  4. Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism.

    Science.gov (United States)

    Cheng, W-F; Chang, M-C; Sun, W-Z; Lee, C-N; Lin, H-W; Su, Y-N; Hsieh, C-Y; Chen, C-A

    2008-07-01

    A novel method for generating an antigen-specific cancer vaccine and immunotherapy has emerged using a DNA vaccine. However, antigen-presenting cells (APCs) have a limited life span, which hinders their long-term ability to prime antigen-specific T cells. Connective tissue growth factor (CTGF) has a role in cell survival. This study explored the intradermal administration of DNA encoding CTGF with a model tumor antigen, human papilloma virus type 16 E7. Mice vaccinated with CTGF/E7 DNA exhibited a dramatic increase in E7-specific CD4(+) and CD8(+) T-cell precursors. They also showed an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with the wild-type E7 DNA. The delivery of DNA encoding CTGF and E7 or CTGF alone could prolong the survival of transduced dendritic cells (DCs) in vivo. In addition, CTGF/E7-transduced DCs could enhance a higher number of E7-specific CD8(+) T cells than E7-transduced DCs. By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy.

  5. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway

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    Onder, Zeynep; Chang, Vivian; Moroianu, Junona, E-mail: moroianu@bc.edu

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP–8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), {sub 76}IRTFQELLF{sub 84}, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. - Highlights: • HPV8 E7 has a leucine-rich NES within its zinc-binding domain that mediates its nuclear export. • CRM1 nuclear export receptor interacts with HPV8 E7 and mediates its export. • Identification of the critical hydrophobic amino acids of the NES of HPV8 E7.

  6. Expression of LIGHT/TNFSF14 Combined with Vaccination against Human Papillomavirus Type 16 E7 Induces Significant Tumor Regression

    Science.gov (United States)

    Kanodia, Shreya; Da Silva, Diane M.; Karamanukyan, Tigran; Bogaert, Lies; Fu, Yang-Xin; Kast, W. Martin

    2010-01-01

    LIGHT, a ligand for the lymphotoxin-beta receptor, establishes lymphoid-like tissues inside tumor sites and recruits naïve T-cells into the tumor. However, whether these infiltrating T-cells are specific for tumor antigens is not known. We hypothesized that therapy with LIGHT can expand functional tumor-specific CD8+ T-cells that can be boosted using HPV16E6E7-Venezuelan Equine Encephalitis Virus Replicon Particles (HPV16-VRP) and that this combined therapy can eradicate HPV16-induced tumors. Our data show that forced expression of LIGHT in tumors results in an increase in expression of interferon gamma (IFNg) and chemottractant cytokines such as IL-1a, MIG and MIP-2 within the tumor and that this tumor microenvironment correlates with an increase in frequency of tumor-infiltrating CD8+ T-cells. Forced expression of LIGHT also results in the expansion of functional T-cells that recognize multiple tumor-antigens, including HPV16 E7, and these T-cells prevent the outgrowth of tumors upon secondary challenge. Subsequent boosting of E7-specific T-cells by vaccination with HPV16-VRP significantly increases their frequency in both the periphery and the tumor, and leads to the eradication of large well-established tumors, for which either treatment alone is not successful. These data establish the safety of Ad-LIGHT as a therapeutic intervention in pre-clinical studies and suggest that patients with HPV16+ tumors may benefit from combined immunotherapy with LIGHT and antigen-specific vaccination. PMID:20460520

  7. Immunogenicity of dendritic cell-based HPV16 E6/E7 peptide vaccines: CTL activation and protective effects

    Czech Academy of Sciences Publication Activity Database

    Indrová, Marie; Reiniš, Milan; Bubeník, Jan; Jandlová, Táňa; Bieblová, Jana; Vonka, V.; Velek, Jiří

    2004-01-01

    Roč. 50, č. 6 (2004), s. 184-193 ISSN 0015-5500 R&D Projects: GA MZd NC7148; GA MZd NR7807; GA ČR GA301/01/0985; GA ČR GA301/04/0492; GA AV ČR KSK5011112 Grant - others:Fogarty International Center(US) D43 TW000233 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV16 E6/E7 peptides * dendritic cell s * cytotoxic lymphocytes Subject RIV: EC - Immunology Impact factor: 0.507, year: 2004

  8. Quantum trigonometric Calogero-Sutherland model, irreducible characters and Clebsch-Gordan series for the exceptional algebra E7

    International Nuclear Information System (INIS)

    Fernandez Nunez, J.; Garcia Fuertes, W.; Perelomov, A.M.

    2005-01-01

    We reexpress the quantum Calogero-Sutherland model for the Lie algebra E 7 and the particular value of the coupling constant κ=1 by using the fundamental irreducible characters of the algebra as dynamical variables. For that, we need to develop a systematic procedure to obtain all the Clebsch-Gordan series required to perform the change of variables. We describe how the resulting quantum Hamiltonian operator can be used to compute more characters and Clebsch-Gordan series for this exceptional algebra

  9. Murine HPV16 E7-expressing transgenic skin effectively emulates the cellular and molecular features of human high-grade squamous intraepithelial lesions

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    Z.K. Tuong

    2018-06-01

    Full Text Available Currently available vaccines prevent HPV infection and development of HPV-associated malignancies, but do not cure existing HPV infections and dysplastic lesions. Persistence of infection(s in immunocompetent patients may reflect induction of local immunosuppressive mechanisms by HPV, providing a target for therapeutic intervention. We have proposed that a mouse, expressing HPV16 E7 oncoprotein under a Keratin 14 promoter (K14E7 mice, and which develops epithelial hyperplasia, may assist with understanding local immune suppression mechanisms that support persistence of HPV oncogene-induced epithelial hyperplasia. K14E7 skin grafts recruit immune cells from immunocompetent hosts, but consistently fail to be rejected. Here, we review the literature on HPV-associated local immunoregulation, and compare the findings with published observations on the K14E7 transgenic murine model, including comparison of the transcriptome of human HPV-infected pre-malignancies with that of murine K14E7 transgenic skin. We argue from the similarity of i the literature findings and ii the transcriptome profiles that murine K14E7 transgenic skin recapitulates the cellular and secreted protein profiles of high-grade HPV-associated lesions in human subjects. We propose that the K14E7 mouse may be an appropriate model to further study the immunoregulatory effects of HPV E7 expression, and can facilitate development and testing of therapeutic vaccines.

  10. Immortalization of normal human embryonic fibroblasts by introduction of either the human papillomavirus type 16 E6 or E7 gene alone.

    Science.gov (United States)

    Yamamoto, Akito; Kumakura, Shin-ichi; Uchida, Minoru; Barrett, J Carl; Tsutsui, Takeki

    2003-09-01

    The ability of the human papillomavirus type 16 (HPV-16) E6 or E7 gene to induce immortalization of normal human embryonic fibroblast WHE-7 cells was examined. WHE-7 cells at 9 population doublings (PD) were infected with retrovirus vectors encoding either HPV-16 E6 or E7 alone or both E6 and E7 (E6/E7). One of 4 isolated clones carrying E6 alone became immortal and is currently at >445 PD. Four of 4 isolated clones carrying E7 alone escaped from crisis and are currently at >330 PD. Three of 5 isolated clones carrying E6/E7 were also immortalized and are currently at >268 PD. The immortal clone carrying E6 only and 2 of the 3 immortal clones carrying E6/E7 expressed a high level of E6 protein, and all the immortal clones carrying E7 alone and the other immortal clone carrying E6/E7 expressed a high level of E7 protein when compared to their mortal or precrisis clones. The immortal clones expressing a high level of E6 or E7 protein were positive for telomerase activity or an alternative mechanism of telomere maintenance, respectively, known as ALT (alternative lengthening of telomeres). All the mortal or precrisis clones were negative for both phenotypes. All the immortal clones exhibited abrogation of G1 arrest after DNA damage by X-ray irradiation. The expression of INK4a protein (p16(INK4a)) was undetectable in the E6-infected mortal and immortal clones, whereas Rb protein (pRb) was hyperphosphorylated only in the immortal clone. The p16(INK4a) protein was overexpressed in all the E7-infected immortal clones and their clones in the pre-crisis period as well as all the E6/E7-infected mortal and immortal clones, but the pRb expression was downregulated in all of these clones. These results demonstrate for the first time to our knowledge that HPV-16 E6 or E7 alone can induce immortalization of normal human embryonic fibroblasts. Inactivation of p16(INK4a)/pRb pathways in combination with activation of a telomere maintenance mechanism is suggested to be necessary for

  11. HPV E6/E7 RNA in situ hybridization signal patterns as biomarkers of three-tier cervical intraepithelial neoplasia grade.

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    Mark F Evans

    Full Text Available Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3 based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL. In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH. Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4, and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3% CIN 1, 22/22 (100% CIN 2 and in 32/32 (100% CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7% showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5% by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: P<0.0001. These data are consistent with productive phase HPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay's high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e

  12. HPV E6/E7 RNA In Situ Hybridization Signal Patterns as Biomarkers of Three-Tier Cervical Intraepithelial Neoplasia Grade

    Science.gov (United States)

    Evans, Mark F.; Peng, Zhihua; Clark, Kelli M.; Adamson, Christine S.-C.; Ma, Xiao-Jun; Wu, Xingyong; Wang, Hongwei; Luo, Yuling; Cooper, Kumarasen

    2014-01-01

    Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: PHPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay’s high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e.g. among young women) or when ‘LSIL vs. HSIL’ assignment is

  13. Regulation of the Wnt/β-Catenin Signaling Pathway by Human Papillomavirus E6 and E7 Oncoproteins

    Directory of Open Access Journals (Sweden)

    Jesus Omar Muñoz Bello

    2015-08-01

    Full Text Available Cell signaling pathways are the mechanisms by which cells transduce external stimuli, which control the transcription of genes, to regulate diverse biological effects. In cancer, distinct signaling pathways, such as the Wnt/β-catenin pathway, have been implicated in the deregulation of critical molecular processes that affect cell proliferation and differentiation. For example, changes in β-catenin localization have been identified in Human Papillomavirus (HPV-related cancers as the lesion progresses. Specifically, β-catenin relocates from the membrane/cytoplasm to the nucleus, suggesting that this transcription regulator participates in cervical carcinogenesis. The E6 and E7 oncoproteins are responsible for the transforming activity of HPV, and some studies have implicated these viral oncoproteins in the regulation of the Wnt/β-catenin pathway. Nevertheless, new interactions of HPV oncoproteins with cellular proteins are emerging, and the study of the biological effects of such interactions will help to understand HPV-related carcinogenesis. Viruses 2015, 7 4735 This review addresses the accumulated evidence of the involvement of the HPV E6 and E7 oncoproteins in the activation of the Wnt/β-catenin pathway.

  14. The HPV16 E7 oncoprotein increases the expression of Oct3/4 and stemness-related genes and augments cell self-renewal

    Energy Technology Data Exchange (ETDEWEB)

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín [Programa de Doctorado en Ciencias Biomédicas, Instituto de Fisiología Celular (IFC), Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, México (Mexico); Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México 07360, México (Mexico); Ocadiz-Delgado, Rodolfo; García-Villa, Enrique [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México 07360, México (Mexico); Bonilla-Delgado, José [Unidad de Investigación, Hospital Juárez de México, Ciudad de México 07760, México (Mexico); Lagunas-Martínez, Alfredo [División de Biología Molecular de Patógenos, CISEI, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México (Mexico); and others

    2016-12-15

    Oct3/4 is a transcription factor involved in maintenance of the pluripotency and self-renewal of stem cells. The E7 oncoprotein and 17β-estradiol (E{sub 2}) are key factors in cervical carcinogenesis. In the present study, we aimed to investigate the effect of the HPV16 E7 oncoprotein and E{sub 2} on the expression pattern of Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and implicate E{sub 2} in the upregulation of these factors in vivo. We also demonstrated that E7 is involved in cell self-renewal, suggesting that the HPV16 E7 oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal capacity of cancer stem cells. -- Graphical abstract: The HPV16 E7 oncoprotein and 17β-estradiol are involved in the upregulation of Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal ability of cancer stem cells in cervical cancer. - Highlights: •The HPV16 E7 oncoprotein enhances cellular proliferation and dedifferentiation. •The E7 oncoprotein induces stemness-related genes expression in vivo and in vitro. •The 17β-estradiol induces stemness-related genes expression in vivo. •The HPV16 E7 oncoprotein is involved in the cell self-renewal of cancer cells.

  15. The HPV16 E7 oncoprotein increases the expression of Oct3/4 and stemness-related genes and augments cell self-renewal

    International Nuclear Information System (INIS)

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín; Ocadiz-Delgado, Rodolfo; García-Villa, Enrique; Bonilla-Delgado, José; Lagunas-Martínez, Alfredo

    2016-01-01

    Oct3/4 is a transcription factor involved in maintenance of the pluripotency and self-renewal of stem cells. The E7 oncoprotein and 17β-estradiol (E 2 ) are key factors in cervical carcinogenesis. In the present study, we aimed to investigate the effect of the HPV16 E7 oncoprotein and E 2 on the expression pattern of Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and implicate E 2 in the upregulation of these factors in vivo. We also demonstrated that E7 is involved in cell self-renewal, suggesting that the HPV16 E7 oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal capacity of cancer stem cells. -- Graphical abstract: The HPV16 E7 oncoprotein and 17β-estradiol are involved in the upregulation of Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal ability of cancer stem cells in cervical cancer. - Highlights: •The HPV16 E7 oncoprotein enhances cellular proliferation and dedifferentiation. •The E7 oncoprotein induces stemness-related genes expression in vivo and in vitro. •The 17β-estradiol induces stemness-related genes expression in vivo. •The HPV16 E7 oncoprotein is involved in the cell self-renewal of cancer cells.

  16. [HPV DNA vaccines expressing recombinant CRT/HPV6bE7 fusion protein inhibit tumor growth and angiogenic activity].

    Science.gov (United States)

    Xu, Yan; Cheng, Hao; Zhao, Ke-Jia; Zhu, Ke-Jian; Zhang, Xing

    2007-11-01

    This paper was to study the angiogenic inhibitory effect and the potential antitumor effect of the constructed recombinant DNA vaccine CRT/HPV6bE7 in vivo. The C57BL/6 mice were vaccinated respectively with recombinant CRT/HPV6bE7 DNA plamids. The inhibitory effects on angiogenesis of generated vaccines in vivo were evaluated by a bFGF-induced angiogenesis assay using the Matrigel kit. To investigate the potential antitumor effect, the mean tumor weights, sizes and tumor appearing times were measured in C57BL/6 mice treated with HPV6bE7-expressing B16 cells. The results indicated that the recombinants CRT180/HPV6bE7 and CRT180 showed strong anti-angiogenic effects in bFGF-induced angiogenesis in vivo. Moreover, CRT180/HPV6bE7 and CRT180 DNA vaccines could significantly inhibit the tumor growth in tumor challenge experiment, and CRT180/HPV6bE7 was superior to other vaccines in delaying tumor formation time, limiting tumor size and weight in tumor protection experiment. In conclusion, recombinant CRT180/HPV6bE7 DNA could elicit a most efficient anti-angiogenic effect and inhibit tumor growth in mice inoculated with DNA vaccines. The antiangiogenic activity of CRT were suggested residing in a domain between CRT 120-180 aa.

  17. Risk

    Science.gov (United States)

    Cole, Stephen R.; Hudgens, Michael G.; Brookhart, M. Alan; Westreich, Daniel

    2015-01-01

    The epidemiologist primarily studies transitions between states of health and disease. The purpose of the present article is to define a foundational parameter for such studies, namely risk. We begin simply and build to the setting in which there is more than 1 event type (i.e., competing risks or competing events), as well as more than 1 treatment or exposure level of interest. In the presence of competing events, the risks are a set of counterfactual cumulative incidence functions for each treatment. These risks can be depicted visually and summarized numerically. We use an example from the study of human immunodeficiency virus to illustrate concepts. PMID:25660080

  18. Renewable energy supply systems in Indonesia. The Activities Implemented Jointly (AIJ) project of the E7 initiative. A case study

    Energy Technology Data Exchange (ETDEWEB)

    Betz, R.

    1999-02-01

    The Renewable Energy Supply System Project, short RESS project, is an Activities Implemented Jointly (AIJ) project carried out by the E7-Initiative combining eight of the world's largest electric utilities of G7 countries (RWE AG Germany is the main coordinator of this project). The first part of the chapter gives a description of the project's background, organisation and different components including the financial aspects and the present state of implementation of the RESS project. The second part presents the evaluation of the project: on the one hand primary objectives will be analysed from the investor's view, on the other hand secondary objectives from a more development co-operation and political point of view. In the final part general problems and especially problems relevant to the further development of the Clean Development Mechanism (CDM) will be summed up. (orig.)

  19. Enhancement of the nonlinear optical absorption of the E7 liquid crystal at the nematic-isotropic transition

    International Nuclear Information System (INIS)

    Gomez, S.L.; Lenart, V.M.; Bechtold, I.H.; Figueiredo Neto, A.M.

    2012-01-01

    We present an experimental study of the nonlinear optical absorption of the eutectic mixture E7 at the nematic-isotropic phase transition by the Z-scan technique, under continuous-wave excitation at 532 nm. In the nematic region, the effective nonlinear optical coefficient P, which vanishes in the isotropic phase, is negative for the extraordinary beam and positive for an ordinary beam. The parameter SNL, whose definition in terms of the nonlinear absorption coefficient follows the definition of the optical-order parameter in terms of the linear dichroic ratio, behaves like an order parameter with critical exponent 0.22 ± 0.05, in good agreement with the tricritical hypothesis for the nematic isotropic transition. (author)

  20. Detection of the E7 transform gene of human papilloma virus type 16 in human oral squamous cell carcinoma.

    Science.gov (United States)

    Wang, J; Li, J; Huang, H; Fu, Y

    1998-12-01

    To determine, with the use of polymerase chain reaction, the prevalence of human papillomavirus (HPV) 16 in 30 patients with primary oral squamous cell carcinoma (OSCC) and 30 healthy control patients. DNA was extracted from freshly frozen tumor tissues of 30 patients with primary oral squamous cell carcinoma and from the oral mucosa of 30 controls. A pair of specific primers of the E7 early gene of HPV 16 were designed. PCR products were run by 1.5% agarose gel and the results of electrophoresis were photographed. HPV 16 was detected in 36.7% (11/30) of oral squamous cell carcinoma patients and 11.1% (4/30) of controls. HPV 16 has a significant association with oral squamous cell carcinoma. However, the role HPV 16 plays in the tumorigenesis of oral cancer and its clinical significance remain to be investigated.

  1. DNA of HPV and antibodies toward the protein E7 of HPV 16 as prediction factors in women with cervical cancer submitted to radiotherapy

    International Nuclear Information System (INIS)

    Bravo, Maria Mercedes; Combita R, Alba Lucia; Molano L, Monica; Gonzalez Florez, Hector; Orozco D, Oscar

    2002-01-01

    The effects of HPV infection on intrinsic tumor cell sensitivity to radiation therapy (RT) are not clear. Antibodies to HPV16-E7 protein are consistently detected in cervical cancer patients, the changes in the levels of these antibodies after RT thus may have prognostic implications. The aim of this study was to evaluate the antibodies to HPV16-E7 protein and the HPV status in cervical cancer patients before and after RT and to correlate these with clinic pathological parameters. Antibodies to peptide E7 and HPV DNA status before and after RT could have prognosis significance for patients with locally advanced uterine cervical carcinoma

  2. Risk

    Science.gov (United States)

    Barshi, Immanuel

    2016-01-01

    Speaking up, i.e. expressing ones concerns, is a critical piece of effective communication. Yet, we see many situations in which crew members have concerns and still remain silent. Why would that be the case? And how can we assess the risks of speaking up vs. the risks of keeping silent? And once we do make up our minds to speak up, how should we go about it? Our workshop aims to answer these questions, and to provide us all with practical tools for effective risk assessment and effective speaking-up strategies..

  3. Recombinant Listeria vaccines containing PEST sequences are potent immune adjuvants for the tumor-associated antigen human papillomavirus-16 E7.

    Science.gov (United States)

    Sewell, Duane A; Shahabi, Vafa; Gunn, George R; Pan, Zhen-Kun; Dominiecki, Mary E; Paterson, Yvonne

    2004-12-15

    Previous work in our laboratory has established that the fusion of tumor-associated antigens to a truncated form of the Listeria monocytogenes virulence factor listeriolysin O (LLO) enhances the immunogenicity and antitumor efficacy of the tumor antigen when delivered by Listeria or by vaccinia. LLO contains a PEST sequence at the NH(2) terminus. These sequences, which are found in eukaryotic proteins with a short cellular half-life, target proteins for degradation in the ubiquitin-proteosome pathway. To investigate whether the enhanced immunogenicity conferred by LLO is due to the PEST sequence, we constructed new Listeria recombinants that expressed the HPV-16 E7 antigen fused to LLO, which either contained or had been deleted of this sequence. We then compared the antitumor efficacy of this set of vectors and found that Listeria expressing the fusion protein LLO-E7 or PEST-E7 were effective at regressing established macroscopic HPV-16 immortalized tumors in syngeneic mice. In contrast, Listeria recombinants expressing E7 alone or E7 fused to LLO from which the PEST sequence had been genetically removed could only slow tumor growth. Because CD8(+) T cell epitopes are generated in the ubiquitin-proteosome pathway, we also investigated the ability of the vaccines to induce E7-specific CD8(+) T cells in the spleen and to generate E7-specific tumor-infiltrating lymphocytes. A strong correlation was observed between CD8(+) T-cell induction and tumor homing and the antitumor efficacy of the Listeria-E7 vaccines. These findings suggest a strategy for the augmentation of tumor antigen-based immunotherapeutic strategies that may be broadly applicable.

  4. Transforming properties of Felis catus papillomavirus type 2 E6 and E7 putative oncogenes in vitro and their transcriptional activity in feline squamous cell carcinoma in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Altamura, Gennaro, E-mail: gennaro.altamura@unina.it [Department of Veterinary Medicine and Animal Productions, General Pathology and Pathological Anatomy Unit, University of Naples Federico II, Via Delpino 1, 80137 Naples (Italy); Corteggio, Annunziata, E-mail: ancorteg@unina.it [Department of Veterinary Medicine and Animal Productions, General Pathology and Pathological Anatomy Unit, University of Naples Federico II, Via Delpino 1, 80137 Naples (Italy); Pacini, Laura, E-mail: PaciniL@students.iarc.fr [Infections and Cancer Biology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon (France); Conte, Andrea, E-mail: andreaconte88@hotmail.it [Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Pansini 5, 80131 Naples (Italy); Pierantoni, Giovanna Maria, E-mail: gmpieran@unina.it [Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Pansini 5, 80131 Naples (Italy); Tommasino, Massimo, E-mail: tommasinom@iarc.fr [Infections and Cancer Biology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon (France); Accardi, Rosita, E-mail: accardir@iarc.fr [Infections and Cancer Biology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon (France); Borzacchiello, Giuseppe, E-mail: borzacch@unina.it [Department of Veterinary Medicine and Animal Productions, General Pathology and Pathological Anatomy Unit, University of Naples Federico II, Via Delpino 1, 80137 Naples (Italy)

    2016-09-15

    Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis. Furthermore, FcaPV2 E7 bound to feline pRb and impaired pRb levels, resulting in upregulation of the downstream pro-proliferative genes Cyclin A and Cdc2. Importantly, we demonstrated mRNA expression of FcaPV2 E2, E6 and E7 in feline SCC samples, strengthening the hypothesis of a causative role in the development of feline SCC. - Highlights: • FcaPV2 E6 binds to and deregulates feline p53 protein. • FcaPV2 E7 binds to and deregulates feline pRb protein. • FcaPV2 oncogenes inhibit UVB-induced apoptosis. • FcaPV2 E6E7 and E7 increase the lifespan of primary cells. • FcaPV2 E2, E6 and E7 are expressed at the mRNA level in feline SCC in vivo.

  5. Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes ▿

    OpenAIRE

    Hyland, Paula L.; McDade, Simon S.; McCloskey, Rachel; Dickson, Glenda J.; Arthur, Ken; McCance, Dennis J.; Patel, Daksha

    2011-01-01

    A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2...

  6. Distribution of human papilloma virus type 16 E6/E7 gene mutation in cervical precancer or cancer: A case control study in Guizhou Province, China.

    Science.gov (United States)

    Yang, Yingjie; Ren, Jie; Zhang, Qizhu

    2016-02-01

    HPV-16 varies geographically and is correlated with cervical cancer genesis and progression. This study aimed to determine the distribution of HPV-16 E6/E7 genetic variation in patients with invasive cervical cancer or precancer in Guizhou Province, China. A case-control study was designed, and the distribution of HPV-16 E6/E7 genetic variation was compared among women with cervical cancer, precancer, and sexually active without cervical lesion. HPV infection was detected through flow-through hybridization and gene chip techniques to determine the prevalence of HPV 16 E6/E7 genetic variation. Among 90 specimens (30 cervical cancer, 30 precancer, 30 controls), 81 were subjected to HPV-16 E6/E7 gene sequencing. The rates of DNA sequence mutation and amino acid mutation were 76.5% (62/81) and 66.7% (54/81), respectively. Both E6 and E7 genes showed higher mutation rate than their prototypes. The prevalence of E6/E7 mutation significantly differed between the cervical cancer and the controls (P prevalent in cervical cancer or precancer than those in the controls. The possible correlation between genetic variation and cancerigenesis may be used to design an HPV vaccine for cervical carcinoma. © 2015 Wiley Periodicals, Inc.

  7. The HPV16 E7 oncoprotein increases the expression of Oct3/4 and stemness-related genes and augments cell self-renewal.

    Science.gov (United States)

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín; Ocadiz-Delgado, Rodolfo; García-Villa, Enrique; Bonilla-Delgado, José; Lagunas-Martínez, Alfredo; Tapia, Jesús Santa-Olalla; Lambert, Paul F; García-Carrancá, Alejandro; Gariglio, Patricio

    2016-12-01

    Oct3/4 is a transcription factor involved in maintenance of the pluripotency and self-renewal of stem cells. The E7 oncoprotein and 17β-estradiol (E 2 ) are key factors in cervical carcinogenesis. In the present study, we aimed to investigate the effect of the HPV16 E7 oncoprotein and E 2 on the expression pattern of Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and implicate E 2 in the upregulation of these factors in vivo. We also demonstrated that E7 is involved in cell self-renewal, suggesting that the HPV16 E7 oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal capacity of cancer stem cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. A non-pathogenic live vector as an efficient delivery system in vaccine design for the prevention of HPV16 E7-overexpressing cancers.

    Science.gov (United States)

    Hosseinzadeh, Sahar; Bolhassani, Azam; Rafati, Sima; Taheri, Tahereh; Zahedifard, Farnaz; Daemi, Amin; Taslimi, Yasaman; Hashemi, Mehrdad; Memarnejadian, Arash

    2013-01-01

    The attenuated or non-pathogenic live vectors have been evolved specifically to deliver DNA into cells as efficient delivery tools in gene therapy. Recently, a non-pathogenic protozoan, Leishmania tarentolae (L.tar) has attracted a great attention. In current study, we used Leishmania expression system (LEXSY) for stable expression of HPV16 E7 linked to different mini-chaperones [N-/C-terminal of gp96] and compared their immunogenicity and protective effects in C57BL/6 mice against TC-1 challenge. TC-1 murine model is primary C57BL/6 mice lung epithelial cells co-transformed with HPV16 E6, HPV16 E7 and ras oncogenes. Our results showed that subcutaneous administration of mice with both the recombinant L.tar-E7-NT (gp96) and L.tar-E7-CT (gp96) led to enhance the levels of IFN-γ and also IgG2a before and after challenge with TC-1. Furthermore, L.tar-E7-CT (gp96) live vaccine indicated significant protective effects as compared to control groups as well as group vaccinated with L.tar-E7. Indeed, the recombinant live vector is capable of eliciting effective humoral and cellular immune responses in mice, but however, further studies are required to increase their efficacy.

  9. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway.

    Science.gov (United States)

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP-8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), 76IRTFQELLF84, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

    Science.gov (United States)

    van de Wall, Stephanie; Walczak, Mateusz; van Rooij, Nienke; Hoogeboom, Baukje-Nynke; Meijerhof, Tjarko; Nijman, Hans W.; Daemen, Toos

    2015-01-01

    The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus. PMID:26343186

  11. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

    Directory of Open Access Journals (Sweden)

    Stephanie van de Wall

    2015-03-01

    Full Text Available The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV targeting human papillomavirus (HPV. Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7 via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

  12. A novel strategy to improve antigen presentation for active immunotherapy in cancer. Fusion of the human papillomavirus type 16 E7 antigen to a cell penetrating peptide

    International Nuclear Information System (INIS)

    Granadillo, Milaid; Torrens, Isis; Guerra, Maribel

    2012-01-01

    Facilitating the delivery of exogenous antigens to antigen-presenting cells, ensuing processing and presentation via the major histocompatibility complex class I and induction of an effective immune response are fundamental for an effective therapeutic cancer vaccine. In this regard, we propose the use of cell-penetrating peptides fused to a tumor antigen. To demonstrate this concept we designed a fusion protein comprising a novel cell-penetrating and immunostimulatory peptide corresponding to residues 32 to 51 of the Limulus anti-lipopolysaccharide factor protein (LALF 32-51 ) linked to human papillomavirus 16 E7 antigen (LALF 32-51 -E7). In this work, we demonstrated that the immunization with LALF 32-51 -E7 using the TC-1 mouse model induces a potent and long-lasting anti-tumor response supported on an effective E7-specific CD8 +T -cell response. The finding that therapeutic immunization with LALF 32-51 or E7 alone, or an admixture of LALF32-51 and E7, does not induce significant tumor reduction indicates that covalent linkage between LALF 32-51 and E7 is required for the anti-tumor effect. These results support the use of this novel cell-penetrating peptide as an efficient means for delivering therapeutic targets into cellular compartments with the induction of a cytotoxic CD8 +T lymphocyte immune response. This approach is promissory for the treatment of tumors associated with the human papillomavirus 16, which is responsible for the 50% of cervical cancer cases worldwide and other malignancies. Furthermore, protein-based vaccines can circumvent the major histocompatibility complex specificity limitation associated with peptide vaccines providing a greater extent in their application

  13. Crystallization and preliminary crystallographic analysis of an Escherichia coli-selected mutant of the nuclease domain of the metallonuclease colicin E7

    International Nuclear Information System (INIS)

    Czene, Anikó; Tóth, Eszter; Gyurcsik, Béla; Otten, Harm; Poulsen, Jens-Christian N.; Lo Leggio, Leila; Larsen, Sine; Christensen, Hans E. M.; Nagata, Kyosuke

    2013-01-01

    An N-terminally truncated mutant of the colicin E7 nuclease domain was crystallized and diffraction data set was collected to 1.6 Å resolution. The metallonuclease colicin E7 is a member of the HNH family of endonucleases. It serves as a bacterial toxin in Escherichia coli, protecting the host cell from other related bacteria and bacteriophages by degradation of their chromosomal DNA under environmental stress. Its cell-killing activity is attributed to the nonspecific nuclease domain (NColE7), which possesses the catalytic ββα-type metal ion-binding HNH motif at its C-terminus. Mutations affecting the positively charged amino acids at the N-terminus of NColE7 (444–576) surprisingly showed no or significantly reduced endonuclease activity [Czene et al. (2013 ▶), J. Biol. Inorg. Chem.18, 309–321]. The necessity of the N-terminal amino acids for the function of the C-terminal catalytic centre poses the possibility of allosteric activation within the enzyme. Precise knowledge of the intramolecular interactions of these residues that affect the catalytic activity could turn NColE7 into a novel platform for artificial nuclease design. In this study, the N-terminal deletion mutant ΔN4-NColE7-C* of the nuclease domain of colicin E7 selected by E. coli was overexpressed and crystallized at room temperature by the sitting-drop vapour-diffusion method. X-ray diffraction data were collected to 1.6 Å resolution and could be indexed and averaged in the trigonal space group P3 1 21 or P3 2 21, with unit-cell parameters a = b = 55.4, c = 73.1 Å. Structure determination by molecular replacement is in progress

  14. Epithelium Expressing the E7 Oncoprotein of HPV16 Attracts Immune-Modulatory Dendritic Cells to the Skin and Suppresses Their Antigen-Processing Capacity.

    Directory of Open Access Journals (Sweden)

    Janin Chandra

    Full Text Available Antigen presenting cells (APCs in skin can promote either antigen-specific effector functions or antigen tolerance, and thus determine clearance or persistence of cutaneous viral infections. Human papillomavirus (HPV infections can persist in squamous epithelium in immunocompetent individuals, and some persisting HPV infections, particularly with HPV16, promote malignant epithelial transformation. Here, we investigate whether local expression of the HPV16 protein most associated with malignant transformation, HPV16-E7, affects the phenotype and function of APC subsets in the skin. We demonstrate an expanded population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell surface markers which express immune-modulatory enzymes and cytokines not expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene expression in keratinocytes attracts new APC subsets to the epidermis. In vivo migration and transport of antigen to the draining lymph node by these APCs is markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by APCs, is significantly impaired. These data suggest that local expression of HPV16-E7 in keratinocytes can contribute to persisting infection with this oncogenic virus, by altering the phenotype and function of local APCs.

  15. In Vitro and In Vivo Synergistic Therapeutic Effect of Cisplatin with Human Papillomavirus16 E6/E7 CRISPR/Cas9 on Cervical Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Shuai Zhen

    2016-12-01

    Full Text Available PURPOSE: Human papillomavirus (HPV type 16 is one of the major etiologic factors of cervical cancer. Our study aims to investigate the potentiality of the antiviral clustered regularly interspaced short palindromic repeat (CRISPR/CRISPR-associated Cas9 system (CRISPR/Cas9 targeting the E6 and E7 oncogenes of HPV16 as a potential chemosensitizer of cisplatin (cis-diaminedichloroplatinum II; CDDP for cervical cancer. METHODS: Specifically, the therapeutic efficacy of combination of CDDP and HPV16 E6 + E7-CRISPR/Cas9 was assessed in cervical cancer cells and cervical cancer xenograft models. RESULTS: In vitro experiments showed that long-term exposure of SiHa cells to the HPV16 E6 + E7-CRISPR/Cas9 induced apoptosis, and its pro-apoptosis effect became more obvious when combined with CDDP. In vivo study found the efficacy of the combination of HPV16 E6 + E7-CRISPR/Cas9 and CDDP were superior to either of the treatments in term of apoptosis induction and metastasis inhibition. CONCLUSION: Collectively, our results suggested that HPV16 E6 + E7-CRISPR/Cas9 could be an effective sensitizer of CDDP chemotherapy in cervical cancer.

  16. Metaloproteinases 1 e 7 e câncer colorretal Metalloproteinases 1 and 7 and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Mário Jucá

    2008-09-01

    Full Text Available A metaloproteinase-1 (MMP-1 e a metaloproteinase-7 (MMP-7 são proteinases da matriz extracelular (MEC, zinco-dependentes, envolvidas no processo inicial da carcinogênese por permitirem a invasão tumoral na célula e promover o processo de metastatização. O polimorfismo dessas proteinases tem sido estudado recentemente com o objetivo de validar susa expressão e/ou atividade como marcador prognóstico. Evidências cumulativas revelam importante papel das MMP's 1 e 7 em diferentes fases da carcinogênese. A MMP-1 tem ação direta sobre a principal proteína da MEC, que é o colágeno do tecido intersticial conectivo. Sua expressão aumentada neste tecido pode indicar alto potencial de disseminação tumoral em diferentes tipos de câncer, incluindo o colorretal. A associação deste aumento da expressão também parece ser verdadeira para a MMP-7.The metalloproteinase-1 (MMP-1 and metalloproteinase-7 (MMP-7 are proteinases of the extracellular matrix (MEC, zinc-dependent, involved in the initial process of carcinogenesis, allowing the invasion by the tumor cell and promoting the process of metastasis. The polymorphism of these proteinases has been studied recently in order to validate its expression and / or activity as a marker prognosis. Evidence shows cumulative important role of MMPs 1 and 7 in different stages of carcinogenesis. The MMP-1 is direct action on the main protein of the MEC, which is the collagen of interstitial connective tissue. Its increased expression in this tissue may indicate high potential for spread in different tumor types of cancer, including colorectal. The association of this increase of expression also appears to be true for MMP-7.

  17. Heterogeneous genetic diversity pattern in Plasmodium vivax genes encoding merozoite surface proteins (MSP) -7E, -7F and -7L.

    Science.gov (United States)

    Garzón-Ospina, Diego; Forero-Rodríguez, Johanna; Patarroyo, Manuel A

    2014-12-13

    The msp-7 gene has become differentially expanded in the Plasmodium genus; Plasmodium vivax has the highest copy number of this gene, several of which encode antigenic proteins in merozoites. DNA sequences from thirty-six Colombian clinical isolates from P. vivax (pv) msp-7E, -7F and -7L genes were analysed for characterizing and studying the genetic diversity of these pvmsp-7 members which are expressed during the intra-erythrocyte stage; natural selection signals producing the variation pattern so observed were evaluated. The pvmsp-7E gene was highly polymorphic compared to pvmsp-7F and pvmsp-7L which were seen to have limited genetic diversity; pvmsp-7E polymorphism was seen to have been maintained by different types of positive selection. Even though these copies seemed to be species-specific duplications, a search in the Plasmodium cynomolgi genome (P. vivax sister taxon) showed that both species shared the whole msp-7 repertoire. This led to exploring the long-term effect of natural selection by comparing the orthologous sequences which led to finding signatures for lineage-specific positive selection. The results confirmed that the P. vivax msp-7 family has a heterogeneous genetic diversity pattern; some members are highly conserved whilst others are highly diverse. The results suggested that the 3'-end of these genes encode MSP-7 proteins' functional region whilst the central region of pvmsp-7E has evolved rapidly. The lineage-specific positive selection signals found suggested that mutations occurring in msp-7s genes during host switch may have succeeded in adapting the ancestral P. vivax parasite population to humans.

  18. A promoter within the E6 ORF of human papillomavirus type 16 contributes to the expression of the E7 oncoprotein from a monocistronic mRNA

    DEFF Research Database (Denmark)

    Glahder, Jacob-Andreas Harald; Hansen, Christina N; Vinther, Jeppe

    2003-01-01

    RNA that encodes E7 as the first open reading frame (ORF) has been identified. We recently identified a transcription initiation site within the E6 ORF of HPV-16 at nt 542. In the present study we have characterized the P542 promoter, which putatively controls monocistronic expression of E7. The monocistronic m...... from nt 226 to 409. Furthermore, the translation initiation of E7 is most abundant from the monocistronic mRNA. We have also shown that the P542 promoter is downregulated by the transcription factor activator protein 4 (AP-4) and the differentiation-dependent factor hSkn-1a, both binding downstream...... of the transcription initiation site. In conclusion, we have found that P542 is a relatively weak promoter compared with P97 and may be downregulated in differentiated epithelial cells....

  19. Novel anti-metastatic action of cidofovir mediated by inhibition of E6/E7, CXCR4 and Rho/ROCK signaling in HPV tumor cells.

    Directory of Open Access Journals (Sweden)

    Abdessamad Amine

    Full Text Available Cervical cancer is frequently associated with HPV infection. The expression of E6 and E7 HPV oncoproteins is a key factor in its carcinogenicity and might also influence its virulence, including metastatic conversion. The cellular mechanisms involved in metastatic spread remain elusive, but pro-adhesive receptors and their ligands, such as SDF-1alpha and CXCR4 are implicated. In the present study, we assessed the possible relationship between SDF-1alpha/CXCR4 signaling, E6/E7 status and the metastatic process. We found that SDF-1alpha stimulated the invasion of E6/E7-positive cancer cell lines (HeLa and TC-1 in Matrigel though CXCR4 and subsequent Rho/ROCK activation. In pulmonary metastatic foci generated by TC-1 cells IV injection a high proportion of cells expressed membrane-associated CXCR4. In both cases models (in vitro and in vivo cell adhesion and invasion was abrogated by CXCR4 immunological blockade supporting a contribution of SDF-1alpha/CXCR4 to the metastatic process. E6 and E7 silencing using stable knock-down and the approved anti-viral agent, Cidofovir decreased CXCR4 gene expression as well as both, constitutive and SDF-1alpha-induced cell invasion. In addition, Cidofovir inhibited lung metastasis (both adhesion and invasion supporting contribution of E6 and E7 oncoproteins to the metastatic process. Finally, potential signals activated downstream SDF-1alpha/CXCR4 and involved in lung homing of E6/E7-expressing tumor cells were investigated. The contribution of the Rho/ROCK pathway was suggested by the inhibitory effect triggered by Cidofovir and further confirmed using Y-27632 (a small molecule ROCK inhibitor. These data suggest a novel and highly translatable therapeutic approach to cervix cancer, by inhibition of adhesion and invasion of circulating HPV-positive tumor cells, using Cidofovir and/or ROCK inhibition.

  20. The combinational effect of E6/E7 siRNA and anti-miR-182 on apoptosis induction in HPV16-positive cervical cells.

    Science.gov (United States)

    Javadi, Hamidreza; Lotfi, Abbas Sahebghadam; Hosseinkhani, Saman; Mehrani, Hossein; Amani, Jafar; Soheili, Zahra Soheila; Hojati, Zahra; Kamali, Mehdi

    2018-06-06

    In the present research, we assumed that reducing the amounts of E6 and E7 oncoproteins by a specific siRNA sequence and recovering p53 and RB proteins, along with the recovery of the FOXO1 protein by applying anti-miR-182, would increase apoptosis and reduce proliferation rate in cancer cells. The HPV16-positive CaSki cervical cancer cell line was used. 48 hours after transfection of siRNA for targeting E6 and E7 oncoproteins and anti-miR-182, expression of its cellular targets p53, p21 and FOXO1 was assessed by real-time PCR, western blot analysis and immunocytofluorescence staining. In all treatments, apoptosis rate and viability were evaluated using Annexin-V-FITC apoptosis detection kits and MTT assays, respectively. Among the designed siRNAs, E6-1 and E7-2 proved the most effective in reducing E6 and E7 expressions by increasing the apoptotic rates to 12.4% and 16%, respectively, after 48 hours. Also, using anti-miR-182 increased apoptotic rate to 12.7% 48 hours after transfection of cervical cancer cells. The combinational use of either E6-1 or E7-2 siRNAs with anti-miR-182 resulted in a rise in apoptosis to 19.3% and 26%, respectively, higher than those obtained from the individual application of either without anti-miR-182. The simultaneous use of siRNA E6-1 and siRNA E7-2 with cisplatin increased sensitivity to cisplatin and reduced the viability of the cancer cells as compared to the use of cisplatin alone. The simultaneous use of cisplatin and anti-miR-182 had no considerable effect on viability or apoptosis rate compared to cisplatin alone.

  1. Rat primary embryo fibroblast cells suppress transformation by the E6 and E7 genes of human papillomavirus type 16 in somatic hybrid cells.

    OpenAIRE

    Miyasaka, M; Takami, Y; Inoue, H; Hakura, A

    1991-01-01

    The E6 and E7 genes of human papillomavirus type 16 (HPV-16) transform established lines of rat cells but not rat cells in primary culture irrespective of the expression of the two genes. The reason for this difference between the susceptibilities of cell lines and primary cells was examined by using hybrid cells obtained by somatic cell fusion of rat cell lines transformed by the E6 and E7 genes of HPV-16 and freshly isolated rat embryo fibroblast cells. In these hybrid cells, transformed ph...

  2. Gene silencing of HPV16 E6/E7 induced by promoter-targeting siRNA in SiHa cells

    OpenAIRE

    Hong, D; Lu, W; Ye, F; Hu, Y; Xie, X

    2009-01-01

    Background: Recently, transcriptional gene silencing induced by small interfering RNA (siRNA) was found in mammalian and human cells. However, previous studies focused on endogenous genes. Methods: In this study, we designed siRNA targeting the promoter of human papillomavirus 16 E6/E7 and transfected it into the cervical cancer cell line, SiHa. E6 and E7 mRNA and protein expression were detected in cells treated by promoter-targeting siRNA. Futhermore, cellular growth, proliferation, apoptos...

  3. A novel HPV 16 L1-based chimeric virus-like particle containing E6 and E7 seroreactive epitopes permits highly specific detection of antibodies in patients with CIN 1 and HPV-16 infection

    Directory of Open Access Journals (Sweden)

    Santiago-Osorio Edelmiro

    2011-02-01

    Full Text Available Abstract Background The presence of IgG antibodies to HPV-16 L1-virus like particles (VLPs in serum has been reported as a result of persistent exposure to the virus and as a marker of disease progression. However, detection of VLP-specific antibodies in sera does not always indicate a malignant lesion as positive results may also be due to a nonmalignant viral infection. Furthermore, malignant lesions are associated with an increased antibody titer for E6 and E7 proteins. The aim of this study was to develop an ELISA using a novel chimeric virus-like particle (cVLP encoding an L1 protein fused with a string of HPV-16 E6 and E7 seroreactive epitopes to its C-terminus to be used for detection of HPV-16 specific antibodies in patients with cervical intraepithelial lesion grade 1 (CIN 1. Results The sera of 30 patients with CIN 1 who also tested positive for HPV-16 DNA and of 30 age-matched normal donors negative for HPV infection were tested for the presence of IgG antibodies specific for either VLP-L1 (HPV-16 L1, gVLP (derived from Gardasil, or cVLP by ELISA. The cVLP-reactive sera yielded two distinct groups of results: (H reactivity levels that presented very strong cVLP-specific titers, and (L reactivity levels with significantly lower titers similar to those obtained with VLP-L1 and gVLP antigens. Additionally, the sera that presented the higher cVLP titers closely matched those that had significantly stronger reactivity to E6 and E7 epitopes. Interestingly, the samples with the highest titers corresponded to patients with the higher numbers of sexual partners and pregnancies. On the other hand only 4 out of the 12 sera that harbored antibodies with VLP neutralizing ability corresponded to the group with high cVLP antibody titers. Conclusion We report for the first time that chimeric particles containing HPV-16 L1 protein fused with E6 and E7 seroreactive epitopes enable much better detection of IgG antibodies in the sera of CIN 1 patients

  4. Repression of MHC class I transcription by HPV16E7 through interaction with a putative RXRβ motif and NF-κB cytoplasmic sequestration

    International Nuclear Information System (INIS)

    Li, Hui; Zhan, TaiLan; Li, Chang; Liu, Mugen; Wang, Qing K.

    2009-01-01

    Down-regulation of transcription of the MHC class I genes in HPV16 tumorigenic cells is partly due to HPV16E7 associated with the MHC class I promoter and repressed chromatin activation. In this study, we further demonstrated that HPV16E7 is physically associated with a putative RXRβ binding motif (GGTCA) of the proximal promoter of the MHC class I genes by using reporter transcriptional assays and chromatin immunoprecipitation assays. Our data also provide evidence that HPV16E7 inhibits TNF-α-induced up-regulation of MHC class I transcription by impaired nuclear translocation of NF-κB. More importantly, CaSki tumor cells treated with TSA and transfected with the constitutively active mutant form of IKK-α (which can activate NF-κB directly) showed a maximal level of up-regulation of MHC-I expression. Taken together, our results suggest that HPV16E7 may employ two independent mechanisms to ensure that either the constitutive or inducible transcription of MHC class I genes is down-regulated.

  5. Fowlpox virus recombinants expressing HPV-16 E6 and E7 oncogenes for the therapy of cervical carcinoma elicit humoral and cell-mediated responses in rabbits.

    Science.gov (United States)

    Radaelli, Antonia; Pozzi, Eleana; Pacchioni, Sole; Zanotto, Carlo; Morghen, Carlo De Giuli

    2010-04-21

    Around half million new cases of cervical cancer arise each year, making the development of an effective therapeutic vaccine against HPV a high priority. As the E6 and E7 oncoproteins are expressed in all HPV-16 tumour cells, vaccines expressing these proteins might clear an already established tumour and support the treatment of HPV-related precancerous lesions. Three different immunisation regimens were tested in a pre-clinical trial in rabbits to evaluate the humoral and cell-mediated responses of a putative HPV-16 vaccine. Fowlpoxvirus (FP) recombinants separately expressing the HPV-16 E6 (FPE6) and E7 (FPE7) transgenes were used for priming, followed by E7 protein boosting. All of the protocols were effective in eliciting a high antibody response. This was also confirmed by interleukin-4 production, which increased after simultaneous priming with both FPE6 and FPE7 and after E7 protein boost. A cell-mediated immune response was also detected in most of the animals. These results establish a preliminary profile for the therapy with the combined use of avipox recombinants, which may represent safer immunogens than vaccinia-based vectors in immuno-compromised individuals, as they express the transgenes in most mammalian cells in the absence of a productive replication.

  6. Fowlpox virus recombinants expressing HPV-16 E6 and E7 oncogenes for the therapy of cervical carcinoma elicit humoral and cell-mediated responses in rabbits

    Directory of Open Access Journals (Sweden)

    Pacchioni Sole

    2010-04-01

    Full Text Available Abstract Background Around half million new cases of cervical cancer arise each year, making the development of an effective therapeutic vaccine against HPV a high priority. As the E6 and E7 oncoproteins are expressed in all HPV-16 tumour cells, vaccines expressing these proteins might clear an already established tumour and support the treatment of HPV-related precancerous lesions. Methods Three different immunisation regimens were tested in a pre-clinical trial in rabbits to evaluate the humoral and cell-mediated responses of a putative HPV-16 vaccine. Fowlpoxvirus (FP recombinants separately expressing the HPV-16 E6 (FPE6 and E7 (FPE7 transgenes were used for priming, followed by E7 protein boosting. Results All of the protocols were effective in eliciting a high antibody response. This was also confirmed by interleukin-4 production, which increased after simultaneous priming with both FPE6 and FPE7 and after E7 protein boost. A cell-mediated immune response was also detected in most of the animals. Conclusion These results establish a preliminary profile for the therapy with the combined use of avipox recombinants, which may represent safer immunogens than vaccinia-based vectors in immuno-compromised individuals, as they express the transgenes in most mammalian cells in the absence of a productive replication.

  7. Expression of Human papillomavirus 16 E7ggg oncoprotein on N- and C-terminus of Potato virus X coat protein in bacterial and plant cells

    Czech Academy of Sciences Publication Activity Database

    Plchová, Helena; Moravec, Tomáš; Hoffmeisterová, Hana; Folwarczna, Jitka; Čeřovská, Noemi

    2011-01-01

    Roč. 77, č. 2 (2011), s. 146-152 ISSN 1046-5928 R&D Projects: GA ČR GA521/09/1525 Institutional research plan: CEZ:AV0Z50380511 Keywords : Bacterial expression * Human papillomavirus * Oncoprotein E7 Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.587, year: 2011

  8. Transformation of tobacco cpDNA with fusion E7GGG/GUS gene and homologous recombination mediated elimination of the marker gene

    Czech Academy of Sciences Publication Activity Database

    Bříza, Jindřich; Vlasák, Josef; Ryba, Š.; Ludvíková, V.; Niedermeierová, Hana

    2013-01-01

    Roč. 27, č. 2 (2013), s. 3644-3648 ISSN 1310-2818 R&D Projects: GA AV ČR IAA500960903 Institutional support: RVO:60077344 Keywords : E7GGG oncogene * chloroplast transformation * marker-free plant * homologous recombination Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.379, year: 2013

  9. Crystallization and preliminary crystallographic analysis of an Escherichia coli-selected mutant of the nuclease domain of the metallonuclease colicin E7

    DEFF Research Database (Denmark)

    Czene, Aniko; Toth, Eszter; Gyurcsik, Bela

    2013-01-01

    The metallonuclease colicin E7 is a member of the HNH family of endonucleases. It serves as a bacterial toxin in Escherichia coli, protecting the host cell from other related bacteria and bacteriophages by degradation of their chromosomal DNA under environmental stress. Its cell-killing activity ....... X-ray diffraction data were collected to 1.6 Å resolution and could be indexed and averaged in the trigonal space group P3121 or P3221, with unit-cell parameters a = b = 55.4, c = 73.1 Å. Structure determination by molecular replacement is in progress.......The metallonuclease colicin E7 is a member of the HNH family of endonucleases. It serves as a bacterial toxin in Escherichia coli, protecting the host cell from other related bacteria and bacteriophages by degradation of their chromosomal DNA under environmental stress. Its cell-killing activity...... is attributed to the nonspecific nuclease domain (NColE7), which possesses the catalytic ββα-type metal ion-binding HNH motif at its C-terminus. Mutations affecting the positively charged amino acids at the N-terminus of NColE7 (444-576) surprisingly showed no or significantly reduced endonuclease activity...

  10. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, M. F.; Duk, J. M.; Burger, M. P.; de Bruijn, H. W.; Stolz, E.; Herbrink, P.

    1999-01-01

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  11. Maintenance of vascular endothelial cell-specific properties after immortalization with an amphotrophic replication-deficient retrovirus containing human papilloma virus 16 E6/E7 DNA

    NARCIS (Netherlands)

    Fontijn, R.; Hop, C.; Brinkman, H. J.; Slater, R.; Westerveld, A.; van Mourik, J. A.; Pannekoek, H.

    1995-01-01

    Primary human vascular endothelial cells were immortalized by the integration of a single DNA copy of an amphotrophic, replication-deficient retrovirus containing the E6/E7 genes of human papilloma virus. To date, the resulting cell lines, designated EC-RF7 and EC-RF24, have been cultured for more

  12. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, MFD; Duk, JM; Burger, MPM; de Bruijn, HWA; Stolz, E; Herbrink, P

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  13. Human papillomavirus E6/E7 oncogenes promote mouse ear regeneration by increasing the rate of wound re-epithelization and epidermal growth.

    Science.gov (United States)

    Valencia, Concepción; Bonilla-Delgado, José; Oktaba, Katarzyna; Ocádiz-Delgado, Rodolfo; Gariglio, Patricio; Covarrubias, Luis

    2008-12-01

    Mammals have limited regeneration capacity. We report here that, in transgenic mice (Tg(bK6-E6/E7)), the expression of the E6/E7 oncogenes of human papilloma virus type 16 (HPV16) under the control of the bovine keratin 6 promoter markedly improves the mouse's capacity to repair portions of the ear after being wounded. Increased repair capacity correlates with an increased number of epidermal proliferating cells. In concordance with the expected effects of the E6 and E7 oncogenes, levels of p53 decreased and those of p16 in epidermal cells increased. In addition, we observed that wound re-epithelization proceeded faster in transgenic than in wild-type animals. After the initial re-epithelization, epidermal cell migration from the intact surrounding tissue appears to be a major contributor to the growing epidermis, especially in the repairing tissue of transgenic mice. We also found that there is a significantly higher number of putative epidermal stem cells in Tg(bK6-E6/E7) than in wild-type mice. Remarkably, hair follicles and cartilage regenerated within the repaired ear tissue, without evidence of tumor formation. We propose that the ability to regenerate ear portions is limited by the capacity of the epidermis to repair itself and grow.

  14. The BPS spectrum of the 4d {N}=2 SCFT's H 1, H 2, D 4, E 6, E 7, E 8

    Science.gov (United States)

    Cecotti, Sergio; Del Zotto, Michele

    2013-06-01

    Extending results of 1112.3984, we show that all rank 1 {N}=2 SCFT's in the sequence H 1, H 2, D 4 E 6, E 7, E 8 have canonical finite BPS chambers containing precisely 2 h(F) = 12(∆ - 1) hypermultiplets. The BPS spectrum of the canonical BPS chambers saturates the conformal central charge c, and satisfies some intriguing numerology.

  15. Enhancement of T cell-mediated and humoral immunity of beta-glucuronidase-based DNA vaccines against HPV16 E7 oncoprotein

    Czech Academy of Sciences Publication Activity Database

    Šmahel, M.; Poláková, I.; Pokorná, D.; Ludvíková, V.; Dušková, M.; Vlasák, Josef

    2008-01-01

    Roč. 33, č. 1 (2008), s. 93-102 ISSN 1019-6439 R&D Projects: GA ČR GA521/05/2092 Institutional research plan: CEZ:AV0Z50510513 Keywords : immunogenicity * anti-E7 vaccines Subject RIV: FD - Oncology ; Hematology Impact factor: 2.234, year: 2008

  16. Biochemical and Structural Analysis of Hormone-sensitive Lipase Homolog EstE7: Insight into the Stabilized Dimerization of HSL-Homolog Proteins

    International Nuclear Information System (INIS)

    Nam, Ki Hyun; Park, Sung Ha; Lee, Won Ho; Hwang, Kwang Yeon

    2010-01-01

    Hormone sensitive lipase (HSL) plays a major role in energy homeostasis and lipid metabolism. Several crystal structures of HSL-homolog proteins have been identified, which has led to a better understanding of its molecular function. HSLhomolog proteins exit as both monomer and dimer, but the biochemical and structural basis for such oligomeric states has not been successfully elucidated. Therefore, we determined the crystal structure of HSL-homolog protein EstE7 from a metagenome library at 2.2 A resolution and characterized the oligomeric states of EstE7 both structurally and biochemically. EstE7 protein prefers the dimeric state in solution, which is supported by its higher enzymatic activity in the dimeric state. In the crystal form, EstE7 protein shows two-types of dimeric interface. Specifically, dimerization via the external β8-strand occurred through tight association between two pseudosymmetric folds via salt bridges, hydrogen bonds and van der Waals interactions. This dimer formation was similar to that of other HSL-homolog protein structures such as AFEST, BEFA, and EstE1. We anticipate that our results will provide insight into the oligomeric state of HSLhomolog proteins

  17. HPV E6/E7 mRNA Testing Is More Specific than Cytology in Post-Colposcopy Follow-Up of Women with Negative Cervical Biopsy

    Science.gov (United States)

    Sørbye, Sveinung Wergeland; Arbyn, Marc; Fismen, Silje; Gutteberg, Tore Jarl; Mortensen, Elin Synnøve

    2011-01-01

    Background In Norway, women with negative or low-grade cervical biopsies (normal/CIN1) are followed up after six months in order to decide on further follow-up or recall for screening at three-year intervals. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures whereas a low risk of high-grade disease among triage negative women assures safety. Materials and Methods At the University Hospital of North Norway, cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in post-colposcopy follow-up of women with negative or low-grade biopsy. In this study, women with negative biopsy after high grade cytology (ASC-H/HSIL) and/or positive HPV mRNA test in the period 2005–2009 were included (n = 520). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as study endpoint. Results Of 520 women with negative or low-grade biopsy, 124 women (23.8%) had CIN2+ in follow-up biopsy. The sensitivity and specificity of the HPV mRNA test were 89.1% (95% CI, 80.1–98.1) and 92.5% (95% CI, 88.2–96.7), respectively. The ratios of sensitivity, specificity and PPV of HPV mRNA testing compared to repeat cytology for finding CIN2+ was 1.05 (95% CI: 0.92–1.21), 1.21 (95% CI: 1.12–1.32), and 1.49 (95% CI: 1.20–1.86), respectively. The PPV of mRNA was 77.3% (95% CI, 59.8–94.8) in women aged 40 or older. Conclusion Women with negative cervical biopsy require follow-up before resumption of routine screening. Post-colposcopy HPV mRNA testing was as sensitive but more specific than post-colposcopy cytology. In addition, the HPV mRNA test showed higher PPV. A positive mRNA test post-colposcopy could justify treatment in women above 40 years. PMID:21998748

  18. Immortalization of Human Fetal Hepatocyte by Ectopic Expression of Human Telomerase Reverse Transcriptase, Human Papilloma Virus (E7) and Simian Virus 40 Large T (SV40 T) Antigen Towards Bioartificial Liver Support.

    Science.gov (United States)

    Giri, Shibashish; Bader, Augustinus

    2014-09-01

    Generation of genetically stable and non-tumoric immortalization cell line from primary cells would be enormously useful for research and therapeutic purposes, but progress towards this goal has so far been limited. It is now universal acceptance that immortalization of human fetal hepatocytes based on recent advances of telomerase biology and oncogene, lead to unlimited population doubling could be the possible source for bioartificial liver device. Immortalization of human fetal hepatocytes cell line by ectopic expression of human telomerase reverse transcriptase (hTERT), human papilloma virus gene (E7) and simian virus 40 large T (SV40 T) antigens is main goal of present study. We used an inducible system containing human telomerase and E7, both of which are cloned into responder constructs controlled by doxycycline transactivator. We characterized the immortalized human fetal hepatocyte cells by analysis of green fluorescent cells (GFP) positive cells using flow cytometry (FACs) cell sorting and morphology, proliferative rate and antigen expression by immunohistochemical analysis. In addition to we analysized lactate formation, glucose consumption, albumin secretion and urea production of immortalized human fetal hepatocyte cells. After 25 attempts for transfection of adult primary hepatocytes by human telomerase and E7 to immortalize them, none of the transfection systems resulted in the production of a stable, proliferating cell line. Although the transfection efficiency was more than 70% on the first day, the vast majority of the transfected hepatocytes lost their signal within the first 5-7 days. The remaining transfected hepatocytes persisted for 2-4 weeks and divided one or two times without forming a clone. After 10 attempts of transfection human fetal hepatocytes using the same transfection system, we obtained one stable human fetal hepatocytes cell line which was able albumin secretion urea production and glucose consumption. We established a

  19. Morphoproteomics, E6/E7 in-situ hybridization, and biomedical analytics define the etiopathogenesis of HPV-associated oropharyngeal carcinoma and provide targeted therapeutic options.

    Science.gov (United States)

    Brown, Robert E; Naqvi, Syed; McGuire, Mary F; Buryanek, Jamie; Karni, Ron J

    2017-08-17

    Human papillomavirus (HPV) has been identified as an etiopathogenetic factor in oropharyngeal squamous cell carcinoma. The HPV E6 and E7 oncogenes are instrumental in promoting proliferation and blocking differentiation leading to tumorigenesis. Although surgical intervention can remove such tumors, the potential for an etiologic field effect with recurrent disease is real. A downstream effector of E7 oncoprotein, enhancer of zeste homolog 2 (EZH2), is known to promote proliferation and to pose a block in differentiation and in turn, could lead to HPV-induced malignant transformation. However, the EZH2 pathway is amenable to low toxicity therapies designed to promote differentiation to a more benign state and prevent recurrent disease by inhibiting the incorporation of HPV into the genome. This is the first study using clinical specimens to demonstrate EZH2 protein expression in oropharyngeal carcinoma (OPC). The study included eight patients with oropharyngeal carcinoma, confirmed p16INK4a- positive by immunohistochemistry (IHC). The tissue expression of E6/E7 messenger RNA (mRNA) was measured by RNAscope® in-situ hybridization technology. Expression of EZH2, Ki-67, and mitotic indices were assessed by morphoproteomic analysis. Biomedical analytics expanded the results with data from Ingenuity Pathway Analysis (IPA) and KEGG databases to construct a molecular network pathway for further insights. Expression of E6 and E7 oncogenes in p16INK4a- positive oropharyngeal carcinoma was confirmed. EZH2 and its correlates, including elevated proliferation index (Ki-67) and mitotic progression were also present. Biomedical analytics validated the relationship between HPV- E6 and E7 and the expression of the EZH2 pathway. There is morphoproteomic and mRNA evidence of the association of p16INK4a-HPV infection with the E6 and E7 oncogenes and the expression of EZH2, Ki-67 and mitotic progression in oropharyngeal carcinoma. The molecular network biology was confirmed by

  20. Upregulation of HPV E6 and E7 genes in human cervix carcinoma cell lines leads to both an increase in radiation resistance and alterations in apoptosis

    International Nuclear Information System (INIS)

    Kamradt, M.; Krueger, E.; McCall, A.; Manker, C.; Rudnick, S.; Erlich, E.; Khodarev, N; Vaughan, A.T.M.

    1996-01-01

    Purpose: Stage I-III cervical cancer is commonly treated with external beam radiotherapy with curative intent. We have shown that the presence of the artificial steroid dexamethasone can increase the radiation resistance of HPV+ve cervical tumors. Dexamethasone treatment enhances cell proliferation by upregulation of HPV 18 E6 and E7 genes through a glucocorticoid responsive element within the HPV promoter region. The goal of this study is to understand the mechanism whereby steroid treatment produces enhanced radioresistance in cervical tumors. Methods: Four cervical tumor cell lines and one squamous carcinoma cell line (SQ-20B) were used. Each cell line was exposed to 0 - 8 Gy of gamma irradiation in the presence or absence of 1 μM dexamethasone (Dx) and assayed for cell survival using a clonogenic assay. Parallel samples were examined by fluorescence microscopy after Triton X-100 permeabilization and propidium iodide staining 1, 2 and 4 days post irradiation. Nuclei containing the characteristic multi-lobular structure and condensed appearance of apoptosis were recorded. To confirm the presence of apoptosis in these cells a terminal deoxynucleotide transferase staining reaction was carried out to label the free DNA ends characteristic of apoptosis. Results: Administration of Dx increased radiation resistance in all HPV+ve E6 and E7 expressing cell lines studied, a similar effect was seen in two additional HPV 18+ve cervical carcinoma cell lines ME180 and MS751 (data not shown). No effect was seen in the HPV-ve cell lines, or C41 K6 containing anti-sense E6 and E7 genes. Introduction of the anti-sense E6 and E7 sequences into C41 did not affect their ability to undergo radiation-induced apoptosis though Dx administration reduced the amount of apoptosis seen. Conversely, Dx treatment of the HeLa cell line increased radioresistance but did not affect the ability of these cells to engage apoptosis. Conclusion: All (5) cervical cell lines studied containing HPV 18

  1. Deriving the largest expected number of elementary particles in the standard model from the maximal compact subgroup H of the exceptional Lie group E7(-5)

    International Nuclear Information System (INIS)

    El Naschie, M.S.

    2008-01-01

    The maximal number of elementary particles which could be expected to be found within a modestly extended energy scale of the standard model was found using various methods to be N = 69. In particular using E-infinity theory the present Author found the exact transfinite expectation value to be =α-bar o /2≅69 where α-bar o =137.082039325 is the exact inverse fine structure constant. In the present work we show among other things how to derive the exact integer value 69 from the exceptional Lie symmetry groups hierarchy. It is found that the relevant number is given by dim H = 69 where H is the maximal compact subspace of E 7(-5) so that N = dim H = 69 while dim E 7 = 133

  2. Efficient expression of Human papillomavirus 16 E7 oncoprotein fused to C-terminus of Tobacco mosaic virus (TMV) coat protein using molecular chaperones in Escherichia coli

    Czech Academy of Sciences Publication Activity Database

    Folwarczna, Jitka; Moravec, Tomáš; Plchová, Helena; Hoffmeisterová, Hana; Čeřovská, Noemi

    2012-01-01

    Roč. 85, č. 1 (2012), s. 152-157 ISSN 1046-5928 R&D Projects: GA ČR GA521/09/1525; GA ČR GAP501/12/1761 Institutional research plan: CEZ:AV0Z50380511 Keywords : Bacterial expression * Human papillomavirus * E7 oncoprotein Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.429, year: 2012

  3. Oncogenes E6-E7 de los Papilomavirus Humanos de alto riesgo detectados por PCR en Biopsias de pene incluidas en parafina

    Directory of Open Access Journals (Sweden)

    I Guerrero

    1999-01-01

    Full Text Available La alta prevalencia del papilomavirus humano (PVH, referida a nivel mundial, en lesiones genitales de ambos sexos, el rol del varón como reservorio pasivo del virus, y el incremento de la mortalidad por cáncer genital en la mujer en nuestro país, motiva la detección y correlación de los oncogenes de los PVH de alto riesgo con la neoplasia de pene. Informamos de diez casos de biopsias de carcinoma escamoso de pene, incluidos en parafina, los cuales fueron investigados para la presencia de los oncogenes E6-E7 de PVH de alto riesgo, utilizando cebadores tipo específico para los PVH -16 y 18, mediante la reacción en cadena de la polimerasa (PCR. El 40% de los casos mostró un producto de amplificación ADN E6-E7 de los PVH estudiados, correspondiendo el 75% de ellos a detección simple por PVH-18 y el 25% presentó detección mixta ADN E6 - E7 del PVH-16 y 18 simultáneamente. El producto de amplificación fue sometido a comprobación por análisis de restricción específico. La prevalencia obtenida de los oncogenes E6-E7 de los PVH de alto riesgo, usando un método tan sensible como la PCR, apoya el rol de estos virus en el proceso de carcinogénesis de la neoplasia de pene.

  4. Prime/boost immunotherapy of HPV16-induced tumors with E7 protein delivered by Bordetella adenylate cyclase and modified vaccinia virus Ankara

    Czech Academy of Sciences Publication Activity Database

    Macková, J.; Stasíková, J.; Kutinová, L.; Mašín, Jiří; Hainz, P.; Šimšová, Marcela; Gabriel, P.; Šebo, Peter; Němečková, P.

    2006-01-01

    Roč. 55, - (2006), s. 39-46 ISSN 0340-7004 R&D Projects: GA AV ČR IBS5020311; GA ČR GA310/04/0004; GA MZd NR8004 Grant - others:GA MZd NC6570 Institutional research plan: CEZ:AV0Z50200510 Keywords : vaccine * hpv-e7 * vaccinia virus Subject RIV: EE - Microbiology, Virology Impact factor: 4.313, year: 2006

  5. Intracellular human papillomavirus E6, E7 mRNA quantification predicts CIN 2+ in cervical biopsies better than Papanicolaou screening for women regardless of age.

    Science.gov (United States)

    Pierry, Deirdre; Weiss, Gerald; Lack, Benjamin; Chen, Victor; Fusco, Judy

    2012-08-01

    Cervical cancer screening in women younger than 30 years relies on cervical cytology because of the poor performance of human papillomavirus (HPV) DNA testing in this age group. To determine the performance of in-cell HPV E6, E7 mRNA quantification (HPV OncoTect) for the detection of high-grade cervical intraepithelial neoplasia in women younger than 30 years. We analyzed 3133 cytology specimens from a screening population of women aged 19-75 years investigate HPV OncoTect as a triage/secondary screening test for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology in women younger than 30 years. Test results were compared to histology in 246 cases. The sensitivity of E6, E7 mRNA was 89% for CIN 2+ and 100% for CIN 3+ lesions in women 30 years and older. In women younger than 30 years, the sensitivity of E6, E7 mRNA for CIN 2+ lesions was 88% for CIN 2+ and 92% for CIN 3+ lesions. Abnormal cytology (≥ASCUS) exhibited a sensitivity of 89% for CIN 2+ and 100% for CIN 3+ in women 30 years and older and 96% sensitivity for CIN 2+ and 93% sensitivity for CIN 3+ in women younger than 30. The specificity of E6, E7 mRNA was >80% for CIN 2+ and CIN 3+ in both groups of women compared to a specificity of abnormal cytology of ASCUS/LSIL triage in women including those younger than 30 years.

  6. HPV-E7 delivered by engineered exosomes elicits a protective CD8⁺ T cell-mediated immune response.

    Science.gov (United States)

    Di Bonito, Paola; Ridolfi, Barbara; Columba-Cabezas, Sandra; Giovannelli, Andrea; Chiozzini, Chiara; Manfredi, Francesco; Anticoli, Simona; Arenaccio, Claudia; Federico, Maurizio

    2015-03-09

    We developed an innovative strategy to induce a cytotoxic T cell (CTL) immune response against protein antigens of choice. It relies on the production of exosomes, i.e., nanovesicles spontaneously released by all cell types. We engineered the upload of huge amounts of protein antigens upon fusion with an anchoring protein (i.e., HIV-1 Nefmut), which is an inactive protein incorporating in exosomes at high levels also when fused with foreign proteins. We compared the immunogenicity of engineered exosomes uploading human papillomavirus (HPV)-E7 with that of lentiviral virus-like particles (VLPs) incorporating equivalent amounts of the same antigen. These exosomes, whose limiting membrane was decorated with VSV-G, i.e., an envelope protein inducing pH-dependent endosomal fusion, proved to be as immunogenic as the cognate VLPs. It is noteworthy that the immunogenicity of the engineered exosomes remained unaltered in the absence of VSV-G. Most important, we provide evidence that the inoculation in mouse of exosomes uploading HPV-E7 induces production of anti-HPV E7 CTLs, blocks the growth of syngeneic tumor cells inoculated after immunization, and controls the development of tumor cells inoculated before the exosome challenge. These results represent the proof-of-concept about both feasibility and efficacy of the Nefmut-based exosome platform for the induction of CD8+ T cell immunity.

  7. IFN-β antiproliferative effect and miRNA regulation in Human Papilloma Virus E6- and E7-transformed keratinocytes.

    Science.gov (United States)

    Chiantore, Maria Vincenza; Mangino, Giorgio; Iuliano, Marco; Zangrillo, Maria Simona; De Lillis, Ilaria; Vaccari, Gabriele; Accardi, Rosita; Tommasino, Massimo; Fiorucci, Gianna; Romeo, Giovanna

    2017-01-01

    Human Papilloma Viruses (HPVs) are the causative agents of cervical cancer although other types of cancers are associated with HPV infection. Type I Interferons can interfere with HPV E6- and/or E7-dependent transformation and can affect microRNA (miRNA) expression. Cancer cells show a specific pattern of miRNA expression and HPVs are able to modulate miRNAs expressed in infected cells. Keratinocytes transduced with E6 and E7 from mucosal HPV-16 or cutaneous HPV-38 (K16 and K38) were studied to analyze the involvement of HPV oncoproteins in the anti-proliferative activity of IFN-β. In view of our previous data showing senescence induction by the cytokine in K38 cells, we observe that IFN-β treatment leads to p53-indipendent apoptosis in K16 cells whereas induces senescence in K16 cells if E6 is silenced and p53 expression is restored. The levels of selected miRNAs, deregulated in K16 and K38 cells, can be modulated by IFN-β when E6 and E7 proteins of HPV-16, but not HPV-38, are expressed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Molecular screening of compounds to the predicted Protein-Protein Interaction site of Rb1-E7 with p53- E6 in HPV

    Science.gov (United States)

    Shaikh, Faraz; Sanehi, Parvish; Rawal, Rakesh

    2012-01-01

    Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. Human Papillomaviruses (HPVs) which are heterogeneous groups of small double stranded DNA viruses are considered as the primary cause of cervical cancer, involved in 90% of all Cervical Cancers. Two early HPV genes, E6 and E7, are known to play crucial role in tumor formation. E6 binds with p53 and prevents its translocation and thereby inhibit the ability of p53 to activate or repress target genes. E7 binds to hypophosphorylated Rb and thereby induces cells to enter into premature S-phase by disrupting Rb-E2F complexes. The strategy of the research work was to target the site of interaction of Rb1 -E7 & p53-E6. A total of 88 compounds were selected for molecular screening, based on comprehensive literature survey for natural compounds with anti-cancer activity. Molecular docking analysis was carried out with Molegro Virtual Docker, to screen the 88 chosen compounds and rank them according to their binding affinity towards the site of interaction of the viral oncoproteins and human tumor suppressor proteins. The docking result revealed that Nicandrenone a member of Withanolides family of chemical compounds as the most likely molecule that can be used as a candidate drug against HPV induced cervical cancer. Abbreviations HPV - Human Papiloma Virus, HTSP - Human Tumor Suppressor Proteins, VOP - Viral oncoproteins. PMID:22829740

  9. The E7-associated cell-surface antigen: a marker for the 11p13 chromosomal deletion associated with aniridia-Wilms tumor.

    OpenAIRE

    Scoggin, C H; Fisher, J H; Shoemaker, S A; Morse, H; Leigh, T; Riccardi, V M

    1985-01-01

    Unbalanced interstitial deletions of the p13 region of human chromosome 11 have been associated with congenital hypoplasia or aplasia of the iris, mental retardation, ambiguous genitalia, and predisposition to Wilms tumor of the kidney. Utilizing somatic cell hybrids containing either the normal or abnormal chromosome 11 from a child with Wilms tumor and aniridia, we previously mapped the E7 cell-surface antigen to the 11p1300-to-11p15.1 region. To localize even further the site of this antig...

  10. UV Radiation Activates Toll-Like Receptor 9 Expression in Primary Human Keratinocytes, an Event Inhibited by Human Papillomavirus 38 E6 and E7 Oncoproteins.

    Science.gov (United States)

    Pacini, Laura; Ceraolo, Maria Grazia; Venuti, Assunta; Melita, Giusi; Hasan, Uzma A; Accardi, Rosita; Tommasino, Massimo

    2017-10-01

    Several lines of evidence indicate that cutaneous human papillomavirus (HPV) types belonging to the beta genus of the HPV phylogenetic tree synergize with UV radiation in the development of skin cancer. Accordingly, the E6 and E7 oncoproteins from some beta HPV types are able to deregulate pathways related to immune response and cellular transformation. Toll-like receptor 9 (TLR9), in addition to playing a role in innate immunity, has been shown to be involved in the cellular stress response. Using primary human keratinocytes as experimental models, we have shown that UV irradiation (and other cellular stresses) activates TLR9 expression. This event is closely linked to p53 activation. Silencing the expression of p53 or deleting its encoding gene affected the activation of TLR9 expression after UV irradiation. Using various strategies, we have also shown that the transcription factors p53 and c-Jun are recruited onto a specific region of the TLR9 promoter after UV irradiation. Importantly, the E6 and E7 oncoproteins from beta HPV38, by inducing the accumulation of the p53 antagonist ΔNp73α, prevent the UV-mediated recruitment of these transcription factors onto the TLR9 promoter, with subsequent impairment of TLR9 gene expression. This study provides new insight into the mechanism that mediates TLR9 upregulation in response to cellular stresses. In addition, we show that HPV38 E6 and E7 are able to interfere with this mechanism, providing another explanation for the possible cooperation of beta HPV types with UV radiation in skin carcinogenesis. IMPORTANCE Beta HPV types have been suggested to act as cofactors in UV-induced skin carcinogenesis by altering several cellular mechanisms activated by UV radiation. We show that the expression of TLR9, a sensor of damage-associated molecular patterns produced during cellular stress, is activated by UV radiation in primary human keratinocytes (PHKs). Two transcription factors known to be activated by UV radiation, p53

  11. Towards realistic D=6, N=2 Kaluza-Klein supergravity on coset E7/SO(12)xSp(1) with chiral fermions

    International Nuclear Information System (INIS)

    Koh, I.G.; Nishino, H.

    1984-08-01

    An SO(10) GUT model with realistic left-handed chiral 16sub(tilde) fermions is obtained from the D=6, N=2 supergravity with matter and gauge couplings on the scalar coset E 7 /SO(12)xSp(1). The six dimensions compactify into (four-dimensional Minkowski space-time) x (two sphere S 2 ) by a monopole on S 2 without any fine-tuning for the four-dimensional cosmological constant. The monopole charge n (when positive) directly gives the number of generations of quarks and leptons. (author)

  12. High Incidence of HPV-Associated Head and Neck Cancers in FA Deficient Mice Is Associated with E7’s Induction of DNA Damage through Its Inactivation of Pocket Proteins

    Science.gov (United States)

    Park, Jung Wook; Shin, Myeong-Kyun; Pitot, Henry C.; Lambert, Paul F.

    2013-01-01

    Fanconi anemia (FA) patients are highly susceptible to solid tumors at multiple anatomical sites including head and neck region. A subset of head and neck cancers (HNCs) is associated with ‘high-risk’ HPVs, particularly HPV16. However, the correlation between HPV oncogenes and cancers in FA patients is still unclear. We previously learned that FA deficiency in mice predisposes HPV16 E7 transgenic mice to HNCs. To address HPV16 E6’s oncogenic potential under FA deficiency in HNCs, we utilized HPV16 E6-transgenic mice (K14E6) and HPV16 E6/E7-bi-transgenic mice (K14E6E7) on genetic backgrounds sufficient or deficient for one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6 mice failed to develop tumor. However, E6 and fancD2-deficiency accelerated E7-driven tumor development in K14E6E7 mice. The increased tumor incidence was more correlated with E7-driven DNA damage than proliferation. We also found that deficiency of pocket proteins, pRb, p107, and p130 that are well-established targets of E7, could recapitulate E7’s induction of DNA damage. Our findings support the hypothesis that E7 induces HPV-associated HNCs by promoting DNA damage through the inactivation of pocket proteins, which explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer. Our results further demonstrate the unexpected finding that FA deficiency does not predispose E6 transgenic mice to HNCs, indicating a specificity in the synergy between FA deficiency and HPV oncogenes in causing HNCs. PMID:24086435

  13. Use of human papillomavirus DNA, E6/E7 mRNA, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men.

    Directory of Open Access Journals (Sweden)

    Nittaya Phanuphak

    Full Text Available Men who have sex with men (MSM are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM.A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43-46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7% and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline.Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.

  14. Lack of Evidence for a Relationship between High Risk Human Papillomaviruses and Breast Cancer in Iranian Patients.

    Science.gov (United States)

    Doosti, Masoud; Bakhshesh, Mehran; Zahir, Shokouh Taghipour; Shayestehpour, Mohammad; Karimi-Zarchi, Mojgan

    2016-01-01

    Whether there is any relationship between human papilloma virus (HPV) and breast carcinoma is not clear. Some previous studies have indicated a possible role in oncogenesis in the breast. In this study, we therefore analyzed the presence of HPV infection in breast tissues of Iranian women from Yazd city. In a cross-sectional study, formalin-fixed paraffin-embedded tissues from 87 patients with breast cancer and 84 cases with breast fibrocystic lesions (control group) were selected from a tissue archive. Grade of tumors and fibrocystic tissues were determined by two pathologists. The nested-PCR method was performed for detection of HPVs in samples. HPV genotypes were determined by sequencing and the phylogenetic tree depicted by MEGA software. Of the 87 women with breast cancer, 22.9% (20 isolates) had positive results for HPV DNA. In the control group no HPV was detected. The HPV genotypes in positive samples were HPV-16 (35%) HPV-18 (15%), HPV-6 (45%) and HPV-11 (5%). The data did not approved a significant correlation between tissue pathology of breast cancer and the HPV genotype frequency. The data did not provide any evidence for a role of high risk HPV types in oncogenesis in the breast.

  15. Human Papillomavirus (HPV) L1 Serum Antibodies and the Risk of Subsequent Oral HPV Acquisition in Men: The HIM Study.

    Science.gov (United States)

    Pierce Campbell, Christine M; Viscidi, Raphael P; Torres, B Nelson; Lin, Hui-Yi; Fulp, William; Abrahamsen, Martha; Lazcano-Ponce, Eduardo; Villa, Luisa L; Kreimer, Aimée R; Giuliano, Anna R

    2016-07-01

    The role of antibody-mediated immunity in preventing newly acquired oral human papillomavirus (HPV) is not well understood. Among 1618 men participating in the HPV Infection in Men (HIM) Study, we evaluated oral rinses for HPV DNA and baseline sera for HPV-6, -11, -16, and -18 L1 antibodies. Thirty percent of men (486) were seropositive for ≥1 HPV type, and 25 men developed incident oral HPV infection (HPV-6 was detected in 7, HPV-11 in 0, HPV-16 in 17, and HPV-18 in 1). Cox models revealed that men with circulating antibodies to HPV-6, -11, -16, or -18 were not less likely to acquire type-specific oral HPV than men without antibodies (hazard ratio for the risk of acquiring HPV-6, -11, -16, or -18, 1.63; 95% confidence interval, .56-4.76). © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  16. Establishment and characterization of murine small cell lung carcinoma cell lines derived from HPV-16 E6/E7 transgenic mice.

    Science.gov (United States)

    Carraresi, Laura; Martinelli, Rosanna; Vannoni, Alessandro; Riccio, Massimo; Dembic, Maja; Tripodi, Sergio; Cintorino, Marcella; Santi, Spartaco; Bigliardi, Elisa; Carmellini, Mario; Rossini, Mara

    2006-01-08

    We have established two murine cell lines derived from Small Cell Lung Carcinomas (SCLCs) developed by HPV-E6/E7 transgenic mice. These cells named PPAP-9 and PPAP-10 were isolated from mice bearing tumors, 9 and 10 months old, respectively. The cells, 5 microm in diameter, express HPV oncoproteins and sustain tumor formation after subcutaneous injection in syngenic mice. A detailed analysis indicated the epithelial origin and the neuroendocrine differentiation of these cells. We showed by confocal immunofluorescence the expression of the epithelial marker cytokeratin 5, whose gene promoter was used to direct the expression of HPV E6/E. Cells express several neuroendocrine markers such as CGRP, MAP-2, Ash1, CgrA, Scg2. The neuroendocrine differentiation of these cells was further confirmed by electron microscopy demonstrating neuropeptides secreting granules in their cytoplasm. Furthermore, in agreement with the altered expression observed in the majority of human SCLC we showed in these cells the absence of both p53 and pRB and a dramatic reduction in the expression of Caveolin-1.

  17. Degradation of Procion Red H-E7B reactive dye by coupling a photo-Fenton system with a sequencing batch reactor

    International Nuclear Information System (INIS)

    Garcia-Montano, Julia; Torrades, Francesc; Garcia-Hortal, Jose A.; Domenech, Xavier; Peral, Jose

    2006-01-01

    A bench-scale study combining photo-Fenton reaction with an aerobic sequencing batch reactor (SBR) to degrade a commercial homo-bireactive dye (Procion Red H-E7B, 250 mg l -1 ) was investigated. The photo-Fenton process was applied as a pre-treatment, avoiding complete mineralisation, just to obtain a bio-compatible water able to be treated by means of the SBR in a second step. In this sense, different Fenton reagent concentrations were assessed by following dye solution biodegradability enhancement (BOD 5 /COD), as well as the toxicity (EC 50 ), DOC, colour (Abs 543.5 ) and H 2 O 2 evolution with photo-Fenton irradiation time. Obtained pre-treated solutions were biologically oxidized in a SBR containing non-acclimated activated sludge. Different hydraulic retention time (HRT) in the bioreactor were tested to attain the maximum organic load removal efficiency. Best results were obtained with 60 min of 10 mg l -1 Fe(II) and 125 mg l -1 H 2 O 2 photo-Fenton pre-treatment and 1 day HRT in SBR

  18. Degradation of Procion Red H-E7B reactive dye by coupling a photo-Fenton system with a sequencing batch reactor

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Montano, Julia [Departament de Quimica, Edifici Cn, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Barcelona (Spain); Torrades, Francesc [Departament d' Enginyeria Quimica, ETSEI de Terrassa (UPC), C/Colom, 11, E-08222 Terrassa, Barcelona (Spain); Garcia-Hortal, Jose A. [Departament d' Enginyeria Textil i Paperera, ETSEI de Terrassa (UPC), C/Colom, 11, E-08222 Terrassa, Barcelona (Spain); Domenech, Xavier [Departament de Quimica, Edifici Cn, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Barcelona (Spain); Peral, Jose [Departament de Quimica, Edifici Cn, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Barcelona (Spain)]. E-mail: jose.peral@uab.es

    2006-06-30

    A bench-scale study combining photo-Fenton reaction with an aerobic sequencing batch reactor (SBR) to degrade a commercial homo-bireactive dye (Procion Red H-E7B, 250 mg l{sup -1}) was investigated. The photo-Fenton process was applied as a pre-treatment, avoiding complete mineralisation, just to obtain a bio-compatible water able to be treated by means of the SBR in a second step. In this sense, different Fenton reagent concentrations were assessed by following dye solution biodegradability enhancement (BOD{sub 5}/COD), as well as the toxicity (EC{sub 50}), DOC, colour (Abs{sub 543.5}) and H{sub 2}O{sub 2} evolution with photo-Fenton irradiation time. Obtained pre-treated solutions were biologically oxidized in a SBR containing non-acclimated activated sludge. Different hydraulic retention time (HRT) in the bioreactor were tested to attain the maximum organic load removal efficiency. Best results were obtained with 60 min of 10 mg l{sup -1} Fe(II) and 125 mg l{sup -1} H{sub 2}O{sub 2} photo-Fenton pre-treatment and 1 day HRT in SBR.

  19. High-risk and low-risk human papilloma virus in association to spontaneous preterm labor: a case-control study in a tertiary center, Egypt.

    Science.gov (United States)

    Mosbah, Alaa; Barakat, Rafik; Nabiel, Yasmin; Barakat, Ghada

    2018-03-01

    This study aimed to detect the correlation between human papillomavirus (HPV) and spontaneous preterm labor in Egyptian women and its association to the human papilloma viral load and MPP2 gene expression. We performed an observational comparative case-control study in Department of Obstetric and Gynecology, Mansoura University Hospitals over women presented with spontaneous preterm labor, besides females admitted for giving birth at full term to detect conserved sequence in HPV-L1 gene (GP5/GP6) followed by genotype detection of high- and low-risk HPVs with quantification of the viral load and the MMP2 gene expression using real-time polymerase chain reaction (PCR). The prevalence of HPV was 18.1% in preterm females, but only 4% in full-term women (p value = 0.019*). Twenty percent were PCR positive for HPV 16 and 40% for HPV 18 whereas none of the control was positive for any of the studied high-risk genotypes. Thirty percent were PCR positive for HPV 6 and 10% were positive for HPV 11. MMP2 gene expression was significantly higher in preterm than full term. Human papilloma viral load was found to be positively correlated to the rate of MMP2 expression and the gestational age was significantly related to the viral load and the rate of expression of MMP2 gene. Human pabilloma virus especially high-risk genotypes was correlated to spontaneous preterm labor in Egyptian females through increasing early expression of MMP2 gene. The time of occurrence of preterm labor was affected by the viral load and so the rate of expression of MMP2 gene.

  20. Anal HPV genotypes and related displasic lesions in Italian and foreign born high-risk males.

    Science.gov (United States)

    Orlando, Giovanna; Beretta, Rosangela; Fasolo, M Michela; Amendola, Antonella; Bianchi, Silvia; Mazza, Francesca; Rizzardini, Giuliano; Tanzi, Elisabetta

    2009-05-29

    Anal intraepithelial neoplasia and anal cancer are closely related to infection from high-risk Human Papilloma Virus (HPV) genotypes. Since HPVs involved in disease progression are reported to vary by geographical regions, this study focuses on HPV genotypes spectrum in 289 males attending a Sexual Transmitted Diseases (STD) unit according to their nationality. Anal cytology, Digene Hybrid Capture Assay (HC2) and HPV genotyping were evaluated in 226 Italian (IT) and 63 foreign born (FB) subjects, recruited between January 2003 and December 2006. FB people were younger (median 32y-IQR 27-35 vs 36y-IQR 31-43, respectively; Mann-Whitney test por=atypical squamous cells of undetermined significance (ASCUS)) on anal cytology (95.0% vs 84.04%) (p=0.032; OR 3.61; 95% CI 1.04-1.23). HPV-16 is by far the most common genotype found in anal cytological samples independently from nationality while differences in distribution of other HPV genotypes were observed. The probability of infection from high-risk HPVs was higher in FB (OR 1.69; 95% CI 1.07-2.68) and is due to a higher rate of HPV-58 (OR 4.98; 95% CI 2.06-12.04), to a lower rate of HPV-11 (OR 0.35; 95% CI 0.16-0.77), to the presence of other high-risk genotypes (HPV-45, HPV-66, HPV-69). Multiple infections rate was high and comparable between IT and FB people. The relative contribution of each HPV genotype in the development of pre-neoplastic disease to an early age in the FB group cannot be argued by this study and more extensive epidemiological evaluations are needed to define the influence of each genotype and the association with the most prevalent high-risk HPVs on cytological intraepithelial lesions development.

  1. HPV16型E6/E7遺伝子発現誘導が正常ヒト線維芽細胞に及ぼす影響の検討

    OpenAIRE

    黄田, 光博; 清水, 久美子; 白澤, 浩; 清水, 文七; 磯野, 可一

    1997-01-01

    HPV16型E6/E7遺伝子発現を亜鉛により誘導可能な正常ヒト線維芽細胞を樹立し, HPV-16型E6/E7がヒト線維芽細胞に及ぼす影響を細胞学的及び分子生物学的に検討した。HPV-16型E6/E7の発現誘導による正常ヒト線維芽細胞の形態変化は観察されなかったが, E6/E7の発現誘導により, 細胞飽和密度の上昇が観察された。またマウス10T1/2細胞で観察されるE6のHMG-I(Y)発現への影響は, ヒト線維芽細胞では見いだされなかったが, E6/E7によりc-mycの発現が誘導されうることが明らかになった。この結果はE6/E7の細胞不死化に及ぼす過程を究明する上で有用であると考えられる。...

  2. Detection of human papillomavirus among women in Laos: feasibility of using filter paper card and prevalence of high-risk types.

    Science.gov (United States)

    Phongsavan, Keokedthong; Gustavsson, Inger; Marions, Lena; Phengsavanh, Alongkone; Wahlström, Rolf; Gyllensten, Ulf

    2012-10-01

    Persistent infection with high-risk (HR) human papillomavirus (HPV) is a well-recognized cause of cervical cancer, but little is known about the situation in Laos. The aims of the study were to determine the prevalence of HR-HPV among Lao women and to evaluate the use of a filter paper card (FTA Elute Micro Card) for collection of cervical cells in the humid tropical climate. This is a cross-sectional study including 1922 women from 3 provinces in Laos. During a gynecological examination, cervical cells were collected and applied to the FTA card followed by HPV typing using a real-time polymerase chain reaction (PCR)-based assay. Overall, 213 of the 1922 women were positive for HR-HPV (11%). The most common type was the group HPV33/52/58 (3%), followed by the single type 16 (2%) and the group 18/45 (1%), respectively. Only 11 cards (0.6%) did not contain a sufficient amount of genomic DNA for polymerase chain reaction-based analysis. The prevalence of HR-HPV infections in Laos is similar to other Asian countries, and 40% of the women with an HR-HPV infection will be target of the present HPV vaccines. The FTA card is suitable for collection of cervical cells for HR-HPV typing in tropical conditions. This information is important for planning and establishing primary and secondary prevention of cervical cancer in Laos.

  3. Prime-boost therapeutic vaccination in mice with DNA/DNA or DNA/Fowlpox virus recombinants expressing the Human Papilloma Virus type 16 E6 and E7 mutated proteins fused to the coat protein of Potato virus X.

    Science.gov (United States)

    Illiano, Elena; Bissa, Massimiliano; Paolini, Francesca; Zanotto, Carlo; De Giuli Morghen, Carlo; Franconi, Rosella; Radaelli, Antonia; Venuti, Aldo

    2016-10-02

    The therapeutic antitumor potency of a prime-boost vaccination strategy was explored, based on the mutated, nontransforming forms of the E6 (E6 F47R ) and E7 (E7 GGG ) oncogenes of Human Papilloma Virus type 16 (HPV16), fused to the Potato virus X (PVX) coat protein (CP) sequence. Previous data showed that CP fusion improves the immunogenicity of tumor-associated antigens and may thus increase their efficacy. After verifying the correct expression of E6 F47R CP and E7 GGG CP inserted into DNA and Fowlpox virus recombinants by Western blotting and immunofluorescence, their combined use was evaluated for therapy in a pre-clinical mouse model of HPV16-related tumorigenicity. Immunization protocols were applied using homologous (DNA/DNA) or heterologous (DNA/Fowlpox) prime-boost vaccine regimens. The humoral immune responses were determined by ELISA, and the therapeutic efficacy evaluated by the delay in tumor appearance and reduced tumor volume after inoculation of syngeneic TC-1* tumor cells. Homologous DNA/DNA genetic vaccines were able to better delay tumor appearance and inhibit tumor growth when DNAE6 F47R CP and DNAE7 GGG CP were administered in combination. However, the heterologous DNA/Fowlpox vaccination strategy was able to delay tumor appearance in a higher number of animals when E6 F47R CP and in particular E7 GGG CP were administered alone. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. The E7 protein of the cottontail rabbit papillomavirus immortalizes normal rabbit keratinocytes and reduces pRb levels, while E6 cooperates in immortalization but neither degrades p53 nor binds E6AP

    International Nuclear Information System (INIS)

    Ganzenmueller, Tina; Matthaei, Markus; Muench, Peter; Scheible, Michael; Iftner, Angelika; Hiller, Thomas; Leiprecht, Natalie; Probst, Sonja; Stubenrauch, Frank; Iftner, Thomas

    2008-01-01

    Human papillomaviruses (HPVs) cause cervical cancer and are associated with the development of non-melanoma skin cancer. A suitable animal model for papillomavirus-associated skin carcinogenesis is the infection of domestic rabbits with the cottontail rabbit papillomavirus (CRPV). As the immortalizing activity of CRPV genes in the natural target cells remains unknown, we investigated the properties of CRPV E6 and E7 in rabbit keratinocytes (RK) and their influence on the cell cycle. Interestingly, CRPV E7 immortalized RK after a cellular crisis but showed no such activity in human keratinocytes. Co-expressed CRPV E6 prevented cellular crisis. The HPV16 or CRPV E7 protein reduced rabbit pRb levels thereby causing rabbit p19 ARF induction and accumulation of p53 without affecting cellular proliferation. Both CRPV E6 proteins failed to degrade rabbit p53 in vitro or to bind E6AP; however, p53 was still inducible by mitomycin C. In summary, CRPV E7 immortalizes rabbit keratinocytes in a species-specific manner and E6 contributes to immortalization without directly affecting p53

  5. Asociación entre la presencia de anticuerpos anti-Ras y anti-VPH16 E4/E7 y lesiones intraepiteliales del cérvix

    Directory of Open Access Journals (Sweden)

    Vázquez-Corzo Sara

    2003-01-01

    Full Text Available OBJETIVO: Determinar si anticuerpos séricos contra E4, E7 y Ras pueden ser utilizados como marcadores de lesiones tempranas del cérvix uterino asociadas al virus del papiloma humano. MATERIAL Y MÉTODOS: Entre marzo de 1999 y abril de 2000 se realizó un estudio sero-epidemiológico de casos y controles en la clínica de displasias del Hospital General Doctor Gea González, en la Ciudad de México, en 116 muestras de suero para evaluar la presencia de anticuerpos anti-E4, E7 y Ras utilizando un ELISA de captura. Se estimaron razones de momios e intervalos de confianza de 95% RESULTADOS: Anticuerpos anti-E7 se asociaron a mujeres con lesiones NIC III, mientras que anticuerpos anti-E4 y anti-Ras fueron más frecuentes en lesiones NIC I-II. Al evaluar el perfil de anticuerpos que presentaron las mujeres, encontramos que a anticuerpos contra dos proteínas predicen la existencia de una lesión NIC I-II, y b la presencia de tres anticuerpos predicen una lesión NIC III. CONCLUSIONES: La detección de anticuerpos séricos contra E4, E7 y Ras en combinación con otras técnicas de diagnóstico, podrían ser de utilidad para detectar oportunamente a mujeres con lesiones tempranas asociadas al Virus del Papiloma Humano y en riesgo de desarrollar cáncer.

  6. Interferon-β induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Jiarong Zhang

    Full Text Available Infection by human papillomavirus (HPV can cause cervical intraepithelial neoplasia (CIN and cancer. Down-regulation of E6 and E7 expression may be responsible for the positive clinical outcomes observed with IFN treatment, but the molecular basis has not been well determined. As miRNAs play an important role in HPV induced cervical carcinogenesis, we hypothesize that IFN-β can regulate the expressions of specific miRNAs in cervical cancer cells, and that these miRNAs can mediate E6 and E7 expression, thus modulate their oncogenic potential. In this study, we found that miR-129-5p to be a candidate IFN-β inducible miRNA. MiR-129-5p levels gradually decrease with the development of cervical intraepithelial lesions. Manipulation of miR-129-5p expression in Hela cells modulates HPV-18 E6 and E7 viral gene expression. Exogenous miR-129-5p inhibits cell proliferation in Hela cells, promotes apoptosis and blocks cell cycle progression in Hela cells. SP1 is a direct target of miR-129-5p in Hela cells. This study is the first report of a cellular miRNA with anti-HPV activity and provides new insights into regulatory mechanisms between the HPV and the IFN system in host cells at the miRNA level.

  7. The epithelial-mesenchymal transition induced by keratinocyte growth conditions is overcome by E6 and E7 from HPV16, but not HPV8 and HPV38: Characterization of global transcription profiles

    International Nuclear Information System (INIS)

    Azzimonti, Barbara; Dell'Oste, Valentina; Borgogna, Cinzia; Mondini, Michele; Gugliesi, Francesca; De Andrea, Marco; Chiorino, Giovanna; Scatolini, Maria; Ghimenti, Chiara; Landolfo, Santo; Gariglio, Marisa

    2009-01-01

    The aim of this study was to evaluate the growth properties of primary human keratinocytes expressing E6 and E7 proteins, which are from either the β- or α-genotypes, under different culture conditions. We demonstrated that keratinocytes expressing E6 and E7, from both HPV8 and 38, irreversibly underwent the epithelial-mesenchymal transition (EMT) when grown on plastic with FAD medium (F12/DMEM/5%FBS). Expression of E6/E7 from HPV16 was capable of fully overcoming the FAD-induced EMT. Immortalization was only observed in HPV16-transduced cell lines, while the more proliferating phenotype of both KerHPV8 and 38 was mainly related to FAD-induced EMT. Microarray analysis of exponentially growing cells identified 146 cellular genes that were differentially regulated in HPV16 compared to HPV8- and 38-transduced cells. A large accumulation of transcripts associated with epidermal development and differentiation was observed in HPV16-transduced cells, whereas transcripts of genes involved in the extracellular matrix, multicellular organismal processes, and inflammatory response were affected in HPV8 and 38-transduced cells.

  8. Human Papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization

    Science.gov (United States)

    Vandermark, Erik R.; Deluca, Krysta A.; Gardner, Courtney R.; Marker, Daniel F.; Schreiner, Cynthia N.; Strickland, David A.; Wilton, Katelynn M.; Mondal, Sumona; Woodworth, Craig D.

    2012-01-01

    The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expression of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone. PMID:22284893

  9. Chromogenic In Situ Hybridization and p16/Ki67 Dual Staining on Formalin-Fixed Paraffin-Embedded Cervical Specimens: Correlation with HPV-DNA Test, E6/E7 mRNA Test, and Potential Clinical Applications

    Directory of Open Access Journals (Sweden)

    Roberta Zappacosta

    2013-01-01

    Full Text Available Although HPV-DNA test and E6/E7 mRNA analyses remain the current standard for the confirmation of human papillomavirus (HPV infections in cytological specimens, no universally adopted techniques exist for the detection of HPV in formalin-fixed paraffin-embedded samples. Particularly, in routine laboratories, molecular assays are still time-consuming and would require a high level of expertise. In this study, we investigated the possible use of a novel HPV tyramide-based chromogenic in situ hybridization (CISH technology to locate HPV on tissue specimens. Then, we evaluate the potential usefulness of p16INK4a/Ki-67 double stain on histological samples, to identify cervical cells expressing HPV E6/E7 oncogenes. In our series, CISH showed a clear signal in 95.2% of the specimens and reached a sensitivity of 86.5%. CISH positivity always matched with HPV-DNA positivity, while 100% of cases with punctated signal joined with cervical intraepithelial neoplasia grade 2 or worse (CIN2+. p16/Ki67 immunohistochemistry gave an interpretable result in 100% of the cases. The use of dual stain significantly increased the agreement between pathologists, which reached 100%. Concordance between dual stain and E6/E7 mRNA test was 89%. In our series, both CISH and p16INK4a/Ki67 dual stain demonstrated high grade of performances. In particular, CISH would help to distinguish episomal from integrated HPV, in order to allow conclusions regarding the prognosis of the lesion, while p16INK4a/Ki67 dual stain approach would confer a high level of standardization to the diagnostic procedure.

  10. Chromogenic In Situ Hybridization and p16/Ki67 Dual Staining on Formalin-Fixed Paraffin-Embedded Cervical Specimens: Correlation with HPV-DNA Test, E6/E7 mRNA Test, and Potential Clinical Applications

    Science.gov (United States)

    Zappacosta, Roberta; Colasante, Antonella; Viola, Patrizia; D'Antuono, Tommaso; Lattanzio, Giuseppe; Capanna, Serena; Gatta, Daniela Maria Pia; Rosini, Sandra

    2013-01-01

    Although HPV-DNA test and E6/E7 mRNA analyses remain the current standard for the confirmation of human papillomavirus (HPV) infections in cytological specimens, no universally adopted techniques exist for the detection of HPV in formalin-fixed paraffin-embedded samples. Particularly, in routine laboratories, molecular assays are still time-consuming and would require a high level of expertise. In this study, we investigated the possible use of a novel HPV tyramide-based chromogenic in situ hybridization (CISH) technology to locate HPV on tissue specimens. Then, we evaluate the potential usefulness of p16INK4a/Ki-67 double stain on histological samples, to identify cervical cells expressing HPV E6/E7 oncogenes. In our series, CISH showed a clear signal in 95.2% of the specimens and reached a sensitivity of 86.5%. CISH positivity always matched with HPV-DNA positivity, while 100% of cases with punctated signal joined with cervical intraepithelial neoplasia grade 2 or worse (CIN2+). p16/Ki67 immunohistochemistry gave an interpretable result in 100% of the cases. The use of dual stain significantly increased the agreement between pathologists, which reached 100%. Concordance between dual stain and E6/E7 mRNA test was 89%. In our series, both CISH and p16INK4a/Ki67 dual stain demonstrated high grade of performances. In particular, CISH would help to distinguish episomal from integrated HPV, in order to allow conclusions regarding the prognosis of the lesion, while p16INK4a/Ki67 dual stain approach would confer a high level of standardization to the diagnostic procedure. PMID:24369532

  11. A pilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+ cervical intraepithelial neoplasia 2/3 (CIN2/3).

    Science.gov (United States)

    Alvarez, Ronald D; Huh, Warner K; Bae, Sejong; Lamb, Lawrence S; Conner, Michael G; Boyer, Jean; Wang, Chenguang; Hung, Chien-Fu; Sauter, Elizabeth; Paradis, Mihaela; Adams, Emily A; Hester, Shirley; Jackson, Bradford E; Wu, T C; Trimble, Cornelia L

    2016-02-01

    The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3. Eligible patients with HPV16(+) CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue. Thirty-two patients with HPV16(+) CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort. pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Human papillomavirus type 6 and 11 genetic variants found in 71 oral and anogenital epithelial samples from Australia.

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    Jennifer A Danielewski

    Full Text Available Genetic variation of 49 human papillomavirus (HPV 6 and 22 HPV11 isolates from recurrent respiratory papillomatosis (RRP (n = 17, genital warts (n = 43, anal cancer (n = 6 and cervical neoplasia cells (n = 5, was determined by sequencing the long control region (LCR and the E6 and E7 genes. Comparative analysis of genetic variability was examined to determine whether different disease states resulting from HPV6 or HPV11 infection cluster into distinct variant groups. Sequence variation analysis of HPV6 revealed that isolates cluster into variants within previously described HPV6 lineages, with the majority (65% clustering to HPV6 sublineage B1 across the three genomic regions examined. Overall 72 HPV6 and 25 HPV11 single nucleotide variations, insertions and deletions were observed within samples examined. In addition, missense alterations were observed in the E6/E7 genes for 6 HPV6 and 5 HPV11 variants. No nucleotide variations were identified in any isolates at the four E2 binding sites for HPV6 or HPV11, nor were any isolates found to be identical to the HPV6 lineage A or HPV11 sublineage A1 reference genomes. Overall, a high degree of sequence conservation was observed between isolates across each of the regions investigated for both HPV6 and HPV11. Genetic variants identified a slight association with HPV6 and anogenital lesions (p = 0.04. This study provides important information on the genetic diversity of circulating HPV 6 and HPV11 variants within the Australian population and supports the observation that the majority of HPV6 isolates cluster to the HPV6 sublineage B1 with anogenital lesions demonstrating an association with this sublineage (p = 0.02. Comparative analysis of Australian isolates for both HPV6 and HPV11 to those from other geographical regions based on the LCR revealed a high degree of sequence similarity throughout the world, confirming previous observations that there are no geographically specific variants for these

  13. Rearrangement of the distal pocket accompanying E7 His → Gln substitution in elephant carbonmonoxy- and oxymyoglobin: 1H NMR identification of a new aromatic residue in the heme pocket

    International Nuclear Information System (INIS)

    Yu, L.P.; La Mar, G.N.; Mizukami, H.

    1990-01-01

    Two-dimensional 1 H NMR methods have been used to assign side-chain resonances for the residues in the distal heme pocket of elephant carbonmonoxymyoglobin (MbCO) and oxymyoglobin (MbO 2 ). It is shown that, while the other residues in the heme pocket are minimally perturbed, the Phe CD4 residue in elephant MbCO and MbO 2 resonates considerably upfield compared to the corresponding residue in sperm whale MbCO. The new NOE connectivities to Val E11 and heme-induced ring current calculations indicate that Phe CD4 has been inserted into the distal heme pocket by reorienting the aromatic side chain and moving the CD corner closer to the heme. The CζH proton of the Phe CD4 was found to move toward the iron of the heme by ∼4 angstrom relative to the position in sperm whale MbCO, requiring minimally a 3-angstrom movement of the CD helical backbone. The significantly altered distal conformation in elephant myoglobin, rather than the single distal E7 substitution, forms a plausible basis for its altered functional properties of lower autoxidation rate, higher redox potential, and increased affinity for CO ligand. These results demonstrate that one-to-one interpretation of amino acid residue substitution (E7 His → Gln) is oversimplified and that conformational changes of substituted proteins which are not readily predicted have to be considered for interpretation of their functional properties

  14. The high-risk HPV infection and urinary system tumor

    Directory of Open Access Journals (Sweden)

    Yang Wenyan

    2018-04-01

    Full Text Available HPV is classified into high-risk and low-risk types depending on its probability of leading to tumorigenesis. Many studies have shown that HPV infection, especially the infection caused by the high-risk type, is always related to prostate cancer, bladder cancer, penile cancer, testicular cancer, and other urinary system tumors. However, previous studies differed in sexual openness and racial genetic susceptibility of the study object, sample size, and experimental methods. Hence, the correlation between high-risk HPV infection and urinary system tumors remains controversial. The early open reading frame of the HPV genome is composed of E1–E7, among which E6 and E7 are the key transfer proteins. The combination of these proteins with oncogene and anti-oncogene may be one of the mechanisms leading to tumorigenesis.

  15. Periodontal pocket as a potential reservoir of high risk human papilloma virus: A pilot study

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    Manjunath Mundoor Dayakar

    2016-01-01

    Full Text Available Aim: Human papilloma viruses (HPVs are small DNA viruses that have been identified in periodontal pocket as well as gingival sulcus. High risk HPVs are also associated with a subset of head and neck carcinomas. HPV detection in periodontium has previously involved DNA detection. This study attempts to: (a Detect the presence or absence of high risk HPV in marginal periodontiun by identifying E6/E7 messenger RNA (mRNA in cells from samples obtained by periodontal pocket scraping. (b Detect the percentage of HPV E6/E7 mRNA in cells of pocket scrapings, which is responsible for producing oncoproteins E6 and E7. Materials and Methods: Pocket scrapings from the periodontal pockets of eight subjects with generalized chronic periodontitis were taken the detection of presence or absence of E6, E7 mRNA was performed using in situ hybridization and flow cytometry. Results: HPV E6/E7 mRNA was detected in four of the eight samples. Conclusion: Presence of high risk human papillomaviruses in periodontal pockets patients of diagnosed with chronic periodontitis, not suffering from head and neck squamous cell carcinoma in the present day could link periodontitis to HPV related squamous cell carcinoma. Prevalence studies are needed detecting the presence of HPV in marginal periodontium as well as prospective studies of HPV positive periodontitis patients are required to explore this possible link.

  16. Risk management

    OpenAIRE

    Mcmanus, John

    2009-01-01

    Few projects are completed on time, on budget, and to their original requirement or specifications. Focusing on what project managers need to know about risk in the pursuit of delivering projects, Risk Management covers key components of the risk management process and the software development process, as well as best practices for risk identification, risk planning, and risk analysis. The book examines risk planning, risk analysis responses to risk, the tracking and modelling of risks, intel...

  17. Sensitivity, Specificity, and Clinical Value of Human Papillomavirus (HPV) E6/E7 mRNA Assay as a Triage Test for Cervical Cytology and HPV DNA Test ▿

    Science.gov (United States)

    Benevolo, Maria; Vocaturo, Amina; Caraceni, Donatella; French, Deborah; Rosini, Sandra; Zappacosta, Roberta; Terrenato, Irene; Ciccocioppo, Lucia; Frega, Antonio; Rossi, Paolo Giorgi

    2011-01-01

    There is evidence that testing for human papillomavirus (HPV) E6/E7 mRNA is more specific than testing for HPV DNA. A retrospective study was carried out to evaluate the performance of the PreTect HPV-Proofer E6/E7 mRNA assay (Norchip) as a triage test for cytology and HPV DNA testing. This study analyzed 1,201 women, 688 of whom had a colposcopy follow-up and 195 of whom had histology-confirmed high-grade intraepithelial neoplasia or worse (CIN2+). The proportion of positive results and the sensitivity and specificity for CIN2+ were determined for HPV mRNA in comparison to HPV DNA and cytology. All data were adjusted for follow-up completeness. Stratified by cytological grades, the HPV mRNA sensitivity was 83% (95% confidence interval [CI] = 63 to 94%) in ASC-US (atypical squamous cells of undetermined significance), 62% (95% CI = 47 to 75%) in L-SIL (low-grade squamous intraepithelial lesion), and 67% (95% CI = 57 to 76%) in H-SIL (high-grade squamous intraepithelial lesion). The corresponding figures were 99, 91, and 96%, respectively, for HPV DNA. The specificities were 82, 76, and 45%, respectively, for HPV mRNA and 29, 13, and 4%, respectively, for HPV DNA. Used as a triage test for ASC-US and L-SIL, mRNA reduced colposcopies by 79% (95% CI = 74 to 83%) and 69% (95% CI = 65 to 74%), respectively, while HPV DNA reduced colposcopies by 38% (95% CI = 32 to 44%) and by 15% (95% CI = 12 to 19%), respectively. As a HPV DNA positivity triage test, mRNA reduced colposcopies by 63% (95% CI = 60 to 66%), having 68% sensitivity (95% CI = 61 to 75%), whereas cytology at the ASC-US+ threshold reduced colposcopies by 23% (95% CI = 20 to 26%), showing 92% sensitivity (95% CI = 87 to 95%). In conclusion, PreTect HPV-Proofer mRNA can serve as a better triage test than HPV DNA to reduce colposcopy referral in both ASC-US and L-SIL. It is also more efficient than cytology for the triage of HPV DNA-positive women. Nevertheless, its low sensitivity demands a strict follow-up of

  18. Human papillomavirus 16 E2-, E6- and E7-specific T-cell responses in children and their mothers who developed incident cervical intraepithelial neoplasia during a 14-year follow-up of the Finnish Family HPV cohort.

    Science.gov (United States)

    Koskimaa, Hanna-Mari; Paaso, Anna E; Welters, Marij J P; Grénman, Seija E; Syrjänen, Kari J; van der Burg, Sjoerd H; Syrjänen, Stina M

    2014-02-13

    Human papillomavirus (HPV) infection has traditionally been regarded as a sexually transmitted disease (STD), but recent evidence implicates that an infected mother can transmit HPV to her newborn during pregnancy, at delivery, perinatal period or later. Given the lack of any studies on HPV-specific immune responses in children, we conducted HPV16-specific cell-mediated immune (CMI) monitoring of the mother-child pairs with known oral and genital HPV follow-up (FU) data since the delivery. In the Finnish Family HPV Study, 10 out of 331 mothers developed incident cervical intraepithelial neoplasia (CIN) during their 14-year FU. Our hypothesis according to the common dogma is that there is no HPV16 specific immune response in offspring of the CIN mother as she/he has not started the sexual life yet. We used overlapping 30-35 mer peptides covering the entire HPV16 E2, E6 and E7 protein sequences. Assays for lymphocyte proliferation capacity, cytokine production and HPV16-specific Foxp3 + CD25 + CD4+ regulatory T-cells were performed. HPV16-specific proliferative T-cell responses were broader in children than in their mothers. Nine of 10 children had responses against both E2 peptide pools compared to only 4 of the 10 mothers. Six of the 10 children and only 2 mothers displayed reactivity to E6 and/or E7. The cytokine levels of IL-2 (p = 0.023) and IL-5 (p = 0.028) induced by all peptide pools, were also higher among children than their mothers. The children of the mothers with incident CIN3 had significantly higher IFN-γ (p = 0.032) and TNF-α (p = 0.008) levels than other children. Our study is the first to show that also children could have HPV-specific immunity. These data indicate that the children have circulating HPV16-specific memory T-cells which might have been induced by previous HPV16 exposure or ongoing HPV 16 infection.

  19. Estimativa de níveis críticos superiores do índice de temperatura e umidade para vacas leiteiras ¹/2, ³/4 e 7/8 Holandês-Zebu em lactação Estimation of upper critical levels of the temperature-humidity index for ½, 3/4 e 7/8 lactating Holstein-Zebu dairy cows

    Directory of Open Access Journals (Sweden)

    Marcílio de Azevedo

    2005-12-01

    Full Text Available A temperatura retal (TR, freqüência respiratória (FR e temperatura da superfície corporal (TS foram avaliadas em vacas ½, ¾ e 7/8 Holandês-Zebu (HZ durante dois verões e dois invernos nos períodos da manhã e da tarde no Município de Coronel Pacheco - MG, Brasil. O objetivo nesta pesquisa foi estimar níveis críticos superiores do índice de temperatura e umidade (ITU para os grupos genéticos pesquisados. As medidas para análise de correlação e de regressão múltipla entre as variáveis foram obtidas de um grupo de 15 vacas em lactação por estação estudada, sendo cinco de cada um dos grupos genéticos ½, ¾ e 7/8HZ. Os resultados obtidos na análise de correlação evidenciaram que a freqüência respiratória (FR é um indicador de estresse térmico melhor que a temperatura retal (TR. Com base na TR, foram estimados valores críticos superiores de ITU iguais a 80, 77 e 75 para os grupos genéticos ½, ¾ e 7/8HZ, respectivamente. Considerando-se a FR, os valores críticos superiores de ITU estimados para os referidos grupos genéticos foram 79, 77 e 76, respectivamente. Com base na TS, estimou-se valor crítico superior de ITU igual a 79 para os três grupos genéticos estudados. Vacas do grupo genético ½HZ demonstraram maior tolerância ao calor que as 7/8HZ, enquanto as ¾HZ se situaram em posição intermediária.The objective of this trial was to estimate the upper critical levels of the temperature-humidity index (TUI measuring morning and afternoon rectal temperature (RT, respiratory rate (RF, and hair coat surface temperature (ST of ½, ¾ and 7/8Holstein-Zebu (HZ dairy cows during two consecutive years (two summers and two winters in Coronel Pacheco, MG, Brazil. Correlation and multiple analysis were determined using data obtained from 15 dairy crossbreed cows/season; five from each genetic group (GG. Results showed that RF was more reliable than RT as an indicator of heat stress based on both correlation and

  20. Concentration risk

    Directory of Open Access Journals (Sweden)

    Matić Vesna

    2016-01-01

    Full Text Available Concentration risk has been gaining a special dimension in the contemporary financial and economic environment. Financial institutions are exposed to this risk mainly in the field of lending, mostly through their credit activities and concentration of credit portfolios. This refers to the concentration of different exposures within a single risk category (credit risk, market risk, operational risk, liquidity risk.

  1. Towards a “Sample-In, Answer-Out” Point-of-Care Platform for Nucleic Acid Extraction and Amplification: Using an HPV E6/E7 mRNA Model System

    Directory of Open Access Journals (Sweden)

    Anja Gulliksen

    2012-01-01

    Full Text Available The paper presents the development of a “proof-of-principle” hands-free and self-contained diagnostic platform for detection of human papillomavirus (HPV E6/E7 mRNA in clinical specimens. The automated platform performs chip-based sample preconcentration, nucleic acid extraction, amplification, and real-time fluorescent detection with minimal user interfacing. It consists of two modular prototypes, one for sample preparation and one for amplification and detection; however, a common interface is available to facilitate later integration into one single module. Nucleic acid extracts (n=28 from cervical cytology specimens extracted on the sample preparation chip were tested using the PreTect HPV-Proofer and achieved an overall detection rate for HPV across all dilutions of 50%–85.7%. A subset of 6 clinical samples extracted on the sample preparation chip module was chosen for complete validation on the NASBA chip module. For 4 of the samples, a 100% amplification for HPV 16 or 33 was obtained at the 1 : 10 dilution for microfluidic channels that filled correctly. The modules of a “sample-in, answer-out” diagnostic platform have been demonstrated from clinical sample input through sample preparation, amplification and final detection.

  2. Synthesis of 4-((1E, 6E)-7-(4-hydroxy-3-methoxyphenyl)-3, 5-dioxohepta-1, 6-dienyl)-2-methoxyphenyl 4-fluorobenzoate, a novel monoester derivative of curcumin, its experimental and theoretical (DFT) studies

    Science.gov (United States)

    Srivastava, Sangeeta; Gupta, Preeti; Amandeep; Singh, Ranvijay Pratap

    2016-04-01

    Curcumin (1), isolated as a major component from the chloroform extract of Curcuma longa was converted to its ester derivative 4-((1E, 6E)-7-(4-hydroxy-3-methoxyphenyl)-3,5-dioxohepta-1,6-dienyl)-2-methoxyphenyl 4-fluorobenzoate (2). The compound has been characterized with the help of 1H, 13C NMR, UV, IR and mass spectrometry. The molecular geometry of synthesized compound was calculated in ground state by Density functional theory (DFT/B3LYP) using 6-31G (d,p) basis set. 1H and 13C NMR chemical shifts were calculated in ground state by using Gauge-Including Atomic Orbital (GIAO) approach and these values were correlated with experimental observations. The electronic properties such as HOMO and LUMO energies were calculated using time dependent Density Functional Theory (TD-DFT). Stability of the molecule as a result of hyper conjugative interactions and electron delocalization were analysed using Natural bond orbital (NBO) analysis. Intramolecular interactions were analysed by AIM (Atom in molecule) approach. Global reactivity descriptors were calculated to study the reactive site within molecule. The vibrational wavenumbers were calculated using DFT method and assigned with the help of potential energy distribution (PED). First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compounds. Molecular electrostatic potential (MEP) analysis has also been carried out.

  3. Interferon-Tau has Antiproliferative effects, Represses the Expression of E6 and E7 Oncogenes, Induces Apoptosis in Cell Lines Transformed with HPV16 and Inhibits Tumor Growth In Vivo

    Science.gov (United States)

    Padilla-Quirarte, Herbey Oswaldo; Trejo-Moreno, Cesar; Fierros-Zarate, Geny; Castañeda, Jhoseline Carnalla; Palma-Irizarry, Marie; Hernández-Márquez, Eva; Burguete-Garcia, Ana Isabel; Peralta-Zaragoza, Oscar; Madrid-Marina, Vicente; Torres-Poveda, Kirvis; Bermúdez-Morales, Victor Hugo

    2016-01-01

    Interferon tau (IFN-τ) is a promising alternative antiviral and immunotherapeutic agent in a wide variety of diseases including infectious, neurodegenerative, autoimmune and cancer due to its low toxicity in comparison with other type I interferon´s. The objective of our study was established the effect of the bovine IFN-τ on human (SiHa) and murine (BMK-16/myc) cells transformed with HPV 16 and evaluates the antitumor effect in a murine tumor model HPV 16 positive. We determine that bovine IFN-τ has antiproliferative effects, pro-apoptotic activity and induces repression of viral E6 and E7 oncogenes (time- and dose-dependent) on human and murine cells transformed with HPV 16 similar to the effects of IFN-β. However, IFN-τ induces greater antiproliferative effect, apoptosis and repression of both oncogenes in BMK-16/myc cells compared to SiHa cells. The differences were explained by the presence and abundance of the type I interferon receptor (IFNAR) in each cell line. On the other hand, we treated groups of tumor-bearing mice (HPV16 positive) with IFN-τ and showed the inhibition tumor growth effect in vivo. Our finding indicates that bovine IFN-τ may be a good candidate for immunotherapy against cervical cancer. PMID:27994659

  4. Clinical and epidemiological correlations between the infection with HPV 16 and HPV 18 and female cervical lesions.

    Science.gov (United States)

    Stoian, M; Repanovici, R; Corniţescu, F

    1995-01-01

    A number of 66 specimens from female cervical lesions were examined for infection with human papillomavirus (HPV) types 6, 11, 16, and 18 by nucleic acid hybridization in dot-blot techniques and 35 sera were tested by the immunodot-blot technique, in order to detect the presence of anti E4 and E7 HPV protein antibodies. The findings were compared with the histologic diagnosis. Fifty-six per cent of specimens contained HPV DNA sequences. In 47% of specimens from cervical carcinoma, HPV 11 was detected in 4 cases, HPV 16 in 21 cases, and HPV 18 in 7 cases. Serum antibodies against HPV 16 E4 and HPV 16 E7 occurred in all the cases of uterine carcinoma, in 4 of 10 cases of CIN I-II, and in 3 of 5 sera obtained from apparently healthy women. The analysis of risk factors disclosed the early onset of sexual activity, a relatively high number of births and abortions before the age of 22 years, the use of oral oestroprogestative contraceptive agents, the presence in anamnesis of genital infections with bacterial flora--Candida albicans, Trichomonas vaginalis, Chlamydia trachomatis, Mycoplasma, etc. Our results showed that HPV typing by nucleic acid hybridization was useful for differentiating low- from high-risk cervical lesions and also tried to elucidate the risk factors associated with HPV infections and progression to malignancy.

  5. Efeito do processamento sobre os níveis de colesterol e 7-cetocolesterol em camarão-rosa Effects of processing on free cholesterol and 7-ketocholesterol concentrations in pink-shrimp

    Directory of Open Access Journals (Sweden)

    Andréa Figueiredo Procópio de Moura

    2002-08-01

    Full Text Available A oxidação do colesterol leva à formação de óxidos biologicamente ativos, capazes de desencadear processos citotóxicos, aterogênicos, mutagênicos e cancerígenos. Durante o processamento, os alimentos são expostos, além do calor, ao oxigênio e a outros fatores desencadeadores da oxidação lipídica, inclusive do colesterol. Os crustáceos, além de possuírem níveis elevados de colesterol, apresentam em sua fração lipídica ácidos graxos com alto grau de insaturação, o que favorece a oxidação do referido esterol. O 7-cetocolesterol tem sido utilizado como indicador da oxidação do colesterol, por ser o óxido formado nos estágios iniciais e em maior quantidade que os demais. O objetivo deste trabalho foi avaliar o efeito do cozimento e da fritura sobre a oxidação do colesterol em camarão-rosa (Penaeus brasiliensis e Penaeus paulensis. O processamento do camarão-rosa, de um modo geral, levou à diminuição das concentrações de colesterol e 7-cetocolesterol livres. A redução observada foi bem maior na fritura do que no cozimento, e mais acentuada para o 7-cetocolesterol. Enquanto os níveis de colesterol foram 10,7 e 24,7% menores, a diminuição do 7-cetocolesterol atingiu 41,5 e 61% no camarão cozido e frito, respectivamente, em relação ao controle. A redução de colesterol e 7-cetocolesterol livres em camarão-rosa processado foi relacionada com a eluição destes compostos nos meios de processamento, água de cozimento e óleo de fritura.Cholesterol oxidation results in the production of oxides that exert a wide range of biological activities such as atherosclerosis, mutagenesis, carcinogenesis and citotoxicity. During cooking foods are exposed to oxygen, heat and other factors that can promote lipid oxidation, including cholesterol oxidation. Because of the presence of polyunsaturated fatty acids and the high levels of cholesterol crustaceous have a great potential for oxide production. 7-ketocholesterol

  6. Detection of HPV and the role of p16INK4A overexpression as a surrogate marker for the presence of functional HPV oncoprotein E7 in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Lardon Filip

    2010-03-01

    Full Text Available Abstract Background Based on the well-recognized etiological role of human papillomavirus (HPV in cervical, anogenital and oropharyngeal carcinogenesis, a potential role of HPV in colorectal carcinogenesis has been suggested. For that reason, the aim of the present study was to investigate the presence of HPV DNA in colorectal carcinomas (CRC and to study overexpression of p16INK4A as a marker for the presence of an active HPV oncoprotein E7. These findings were correlated with clinical and pathological prognostic factors of CRC. Methods The presence of HPV was assessed using a multiplex PCR system of 10 non-biotinylated primers. The amplified fragments of HPV positive samples were further analyzed by a highly sensitive, broad spectrum SPF10 PCR and subsequently genotyped using reverse hybridization in a line probe assay. P16INK4A protein expression was investigated in a subset of 90 (30 HPV positive and 60 HPV negative CRC samples by immunohistochemistry. Results HPV DNA was found in 14.2% of the CRC samples with HPV16 as the most prevalent type. No significant differences in clinical and pathological variables were found between HPV positive and negative CRCs, except for age. HPV positive patients were significantly younger (p = 0.05. There was no significant correlation between the presence of HPV and overexpression of p16INK4A (p = 0.325. Conclusions In conclusion, the presence of oncogenic HPV DNA in a small cohort of CRC samples may suggest that HPV may be involved in the carcinogenesis of some CRC. However, contrary to what has been observed in head and neck squamous cell cancer and cancer of the uterine cervix, p16INK4A does not seem to be a surrogate marker for an active HPV infection in CRC. Therefore, further functional analyses are necessary to elucidate the role of HPV in CRC.

  7. The Curcumin Analogue 1,5-Bis(2-hydroxyphenyl-1,4-pentadiene-3-one Induces Apoptosis and Downregulates E6 and E7 Oncogene Expression in HPV16 and HPV18-Infected Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Felicia Paulraj

    2015-06-01

    Full Text Available In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. Determination of their EC50 values indicated relatively higher potency of 1,5-bis(2-hydroxyphenyl-1,4-pentadiene-3-one (MS17, 1.03 ± 0.5 μM; 2.6 ± 0.9 μM and 1,5-bis(4-hydroxy-3-methoxyphenyl-1,4-pentadiene-3-one (MS13, 2.8 ± 0.4; 6.7 ± 2.4 μM in CaSki and HeLa, respectively, with significantly greater growth inhibition at 48 and 72 h of treatment compared to the other analogues or curcumin. Based on cytotoxic and anti-proliferative activity, MS17 was selected for comprehensive apoptotic studies. At 24 h of treatment, fluorescence microscopy detected that MS17-exposed cells exhibited significant morphological changes consistent with apoptosis, corroborated by an increase in nucleosomal enrichment due to DNA fragmentation in HeLa and CaSki cells and activation of caspase-3 activity in CaSki cells. Quantitative real-time PCR also detected significant down-regulation of HPV18- and HPV16-associated E6 and E7 oncogene expression following treatment. The overall data suggests that MS17 treatment has cytotoxic, anti-proliferative and apoptosis-inducing potential in HPV-positive cervical cancer cells. Furthermore, its role in down-regulation of HPV-associated oncogenes responsible for cancer progression merits further investigation into its chemotherapeutic role for cervical cancer.

  8. Comparison of HPV detection technologies: Hybrid capture 2, PreTect HPV-Proofer and analysis of HPV DNA viral load in HPV16, HPV18 and HPV33 E6/E7 mRNA positive specimens.

    LENUS (Irish Health Repository)

    Keegan, Helen

    2012-02-01

    Human papillomavirus (HPV) testing using molecular methods in liquid based cytology (LBC) specimens may be useful as an adjunct to cervical screening by cytology. We compared the positivity rate of the commercially available HPV DNA method hybrid capture 2 (hc2) and the commercially available E6\\/E7 mRNA method PreTect HPV-Proofer in cytological specimens (n=299). LBC specimens collected (n=299) represented the following cervical cytological disease categories: Normal (n=60), borderline nuclear abnormalities (BNA) (n=34), CIN1 (n=121), CIN2 (n=60), CIN3 (n=24). Overall, 69% (205\\/299) of the cases were positive by hc2 and 38% (112\\/299) of the cases were positive by PreTect HPV-Proofer. Concordance rates between the two tests were highest in the high-grade cytology cases (CIN2: 67% and CIN3: 83%) and the normal cytology cases (88%) and lowest in the BNA and CIN1 categories (56% and 52%). HPV DNA viral load analyses were carried out on HPV16 (n=55), HPV18 (n=9) and HPV33 (n=13) samples that were positive by PreTect HPV-Proofer. The sensitivity and specificity of PreTect HPV-Proofer and the hc2 DNA test for the detection of high-grade cytology (i.e. CIN2+) were 71.4% and 75.8% vs 100% and 43.7%, respectively. The relatively low detection rate observed by PreTect HPV-Proofer in the whole range of cytological positive cases, combined with a relatively higher specificity and PPV, suggests that PreTect HPV-Proofer may be more useful than hc2 for triage and in predicting high-grade disease.

  9. Performance of ProEx C and PreTect HPV-Proofer E6/E7 mRNA tests in comparison with the hybrid capture 2 HPV DNA test for triaging ASCUS and LSIL cytology.

    Science.gov (United States)

    Alaghehbandan, Reza; Fontaine, Daniel; Bentley, James; Escott, Nicholas; Ghatage, Prafull; Lear, Adrian; Coutlee, Francois; Ratnam, Samuel

    2013-09-01

    The clinical usefulness of the ProEx C (Becton Dickinson) and PreTect HPV-Proofer E6/E7 mRNA tests (Proofer; Norchip) for the triage of ASCUS and LSIL cytology was determined in comparison with the Hybrid Capture 2 HPV DNA test (HC2; Qiagen). The study population consisted of women with a history of abnormal cytology referred to colposcopy. Histology-confirmed CIN 2+ served as the disease endpoint. The study was based on 1,360 women (mean age 30.7 years), of whom 380 had CIN 2+. Among 315 with ASCUS (CIN 2+, n = 67), the sensitivities of ProEx C, Proofer, and HC2 to detect CIN 2+ were, 71.6, 71.6, and 95.5%, respectively, with a corresponding specificity of 74.6, 74.2, and 35.1%. Among 363 with LSIL (CIN 2+, n = 108), the sensitivities of ProEx C, Proofer, and HC2 were, 67.6, 74.1, and 96.3%, respectively, with a corresponding specificity of 60, 68.2, and 18.4%. Among 225 HC2-positive ASCUS (CIN 2+, n = 64), 105 tested positive by ProEx C, reducing colposcopy referral by 53.3% and detecting 71.9% of CIN 2+; Proofer was positive in 112/225, reducing colposcopy referral by 50.2% and detecting 75.0% of CIN 2+. Among 312 HC2-positive LSIL (CIN 2+, n = 104), 160 tested positive by ProEx C, reducing coloposcopy referral by 48.7% and detecting 66.3% of CIN 2+; Proofer was positive in 159/312, reducing colposcopy referral by 49.0% and detecting 75.0% of CIN 2+. In conclusion, both ProEx C and Proofer have a similar performance profile with a significantly higher specificity but lower sensitivity than HC2 for the detection of CIN 2+. Consequently, although they can reduce colposcopy referral, they will miss a proportion of CIN 2+ cases. This is a major limitation and should be taken into account if these tests are considered for ASCUS or LSIL triage. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

  10. Risk assessment

    International Nuclear Information System (INIS)

    1983-01-01

    The report is in sections, entitled: preface; summary and conclusions; introduction (historical and organizational); estimating engineering risks (techniques of risk estimation and forms of expression of risk); laboratory experiments for estimation of biological risks; estimation of risk from observations on man (travel, medical procedures; occupations; sport); the perception of risks; (as an example of attitudes towards a single hazard, studies of nuclear power are considered among other topics in this section); risk management (estimation; perception; acceptability, analysis of risk, costs and benefits; safety standards; decision-making process; possible guidelines). (U.K.)

  11. Partial pressure (or fugacity) of carbon dioxide, pH, salinity and other variables collected from time series observations using Bubble type equilibrator for autonomous carbon dioxide (CO2) measurement, Carbon dioxide (CO2) gas analyzer and other instruments from MOORING_CHUUKK1_152E_7N in the North Pacific Ocean from 2011-11-18 to 2015-11-28 (NCEI Accession 0157443)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0157443 includes chemical, meteorological, physical and time series data collected from MOORING_CHUUKK1_152E_7N in the North Pacific Ocean from...

  12. Surrounding Risks

    Directory of Open Access Journals (Sweden)

    Mogens Steffensen

    2013-05-01

    Full Text Available Research in insurance and finance was always intersecting although they were originally and generally viewed as separate disciplines. Insurance is about transferring risks between parties such that the burdens of risks are borne by those who can. This makes insurance transactions a beneficial activity for the society. It calls on detection, modelling, valuation, and controlling of risks. One of the main sources of control is diversification of risks and in that respect it becomes an issue in itself to clarify diversifiability of risks. However, many diversifiable risks are not, by nature or by contract design, separable from non-diversifiable risks that are, on the other hand, sometimes traded in financial markets and sometimes not. A key observation is that the economic risk came before the insurance contract: Mother earth destroys and kills incidentally and mercilessly, but the uncertainty of economic consequences can be more or less cleverly distributed by the introduction of an insurance market.

  13. Risk analysis

    International Nuclear Information System (INIS)

    Correa Lizarazu, X.

    2013-01-01

    The power point presentation Colombia risk evaluation experiences, sanitarian regulations evolution, chemical dangers food, biological dangers food, codex alimentarius, trade, industrial effects, dangers identification, data collection and risk profile

  14. Risk Factors

    Science.gov (United States)

    ... cells do not invade nearby tissues or spread. Risk Factors Key Points Factors That are Known to ... chemicals . Factors That are Known to Increase the Risk of Cancer Cigarette Smoking and Tobacco Use Tobacco ...

  15. Technological risks

    International Nuclear Information System (INIS)

    Klinke, A.; Renn, O.

    1998-01-01

    The empirical part about the technological risks deals with different technologies: nuclear energy, early warning systems of nuclear weapons and NBC-weapons, and electromagnetic fields. The potential of damage, the contemporary management strategies and the relevant characteristics will be described for each technology: risks of nuclear energy; risks of early warning systems of nuclear weapons and NBC-weapons; risks of electromagnetic fields. (authors)

  16. Technological risks

    Energy Technology Data Exchange (ETDEWEB)

    Klinke, A.; Renn, O. [Center of Technology Assessment in Baden-Wuerttemberg, Stuttgart (Germany)

    1998-07-01

    The empirical part about the technological risks deals with different technologies: nuclear energy, early warning systems of nuclear weapons and NBC-weapons, and electromagnetic fields. The potential of damage, the contemporary management strategies and the relevant characteristics will be described for each technology: risks of nuclear energy; risks of early warning systems of nuclear weapons and NBC-weapons; risks of electromagnetic fields. (authors)

  17. Climatic risks

    International Nuclear Information System (INIS)

    Lamarre, D.; Favier, R.; Bourg, D.; Marchand, J.P.

    2005-04-01

    The climatic risks are analyzed in this book under the cross-vision of specialists of different domains: philosophy, sociology, economic history, law, geography, climatology and hydrology. The prevention of risks and the precautionary principle are presented first. Then, the relations between climatic risk and geography are analyzed using the notion of territoriality. The territory aspect is in the core of the present day debates about the geography of risks, in particular when the links between climate change and public health are considered. Then the main climatic risks are presented. Droughts and floods are the most damaging ones and the difficulties of prevention-indemnification coupling remain important. (J.S.)

  18. Risk management.

    Science.gov (United States)

    Chambers, David W

    2010-01-01

    Every plan contains risk. To proceed without planning some means of managing that risk is to court failure. The basic logic of risk is explained. It consists in identifying a threshold where some corrective action is necessary, the probability of exceeding that threshold, and the attendant cost should the undesired outcome occur. This is the probable cost of failure. Various risk categories in dentistry are identified, including lack of liquidity; poor quality; equipment or procedure failures; employee slips; competitive environments; new regulations; unreliable suppliers, partners, and patients; and threats to one's reputation. It is prudent to make investments in risk management to the extent that the cost of managing the risk is less than the probable loss due to risk failure and when risk management strategies can be matched to type of risk. Four risk management strategies are discussed: insurance, reducing the probability of failure, reducing the costs of failure, and learning. A risk management accounting of the financial meltdown of October 2008 is provided.

  19. Risk factors

    International Nuclear Information System (INIS)

    Dennery, M.; Dupont, M.A.

    2007-01-01

    This article deals with the development of risk management in the gas sector business: why a risk factor legal mention must precede any published financial information? Do gas companies have to face new risks? Is there specific risks bound to gas activities? Why companies want to master their risks? Is it mandatory or just a new habit? Do they expect a real benefit in return? These are the risk management questions that are analyzed in this article which is based on the public communication of 15 gas companies randomly selected over the world. The information comes from their annual reports or from documents available on their web sites. The intention of this document is not to be exhaustive or to make statistics but only to shade light on the risk factors of the gas sector. (J.S.)

  20. Risk assessment for the transportation of radioactive zeolite liners

    International Nuclear Information System (INIS)

    Gallucci, R.H.V.

    1982-01-01

    The accident risk is estimated for the shipment of two zeolite liners containing radioactive cesium and strontium. Each liner, assumed to hold 68,200 Ci and sealed inside a CNS 1 to 13C, type-B shipping cask, is transported by truck over a 4200-km route. The risk to the population along the route is calculated for potential transportation accidents involving fire, impact, and puncture forces. The total risk is 5.3E-7 man-rem (50-year inhalation dose) and the maximum dose (from the least-likely accident) is 0.7 man-rem. Both estimates are less than 0.1% of comparable risk measures for natural background radiation and spent fuel shipment accidents

  1. Industrial risks

    International Nuclear Information System (INIS)

    Okrent, D.

    1981-01-01

    A brief look is taken at the status of progress, or the lack of it, towards a quantitative approach to the estimation and assessment of risk for several technologies in the United States. The increase of interest in the consideration of comparative risks in decision-making is also discussed. Finally, a recently proposed trial approach to quantitative safety goals for light-water nuclear power reactors is summarized. The approach is divided into two major tasks: the predominantly social and political task of setting safety criteria, and the technical task of estimating the risks and deciding whether the safety criteria have been met. The safety criteria include the following: limits on hazard states within the reactor; limits on risk to the individual; limits on societal risk; a cost-effectiveness criterion as low as reasonably achievable; a small element of risk aversion. (author)

  2. Risk assessment

    International Nuclear Information System (INIS)

    Kinchin, G.H.

    1983-01-01

    After defining risk and introducing the concept of individual and societal risk, the author considers each of these, restricting considerations to risk of death. Some probabilities of death arising from various causes are quoted, and attention drawn to the care necessary in making comparisons between sets of data and to the distinction between voluntary and involuntary categories and between early and delayed deaths. The presentation of information on societal risk is discussed and examples given. The history of quantified risk assessment is outlined, particularly related to the nuclear industry, the process of assessing risk discussed: identification of hazard causes, the development of accident chains and the use of event trees, the evaluation of probability through the collection of data and their use with fault trees, and the assessment of consequences of hazards in terms of fatalities. Reference is made to the human element and common-made failures, and to studies supporting the development of reliability assessment techniques. Acceptance criteria are discussed for individual and societal risk in the nuclear field, and it is shown that proposed criteria lead to risks conservative by comparison with risks from day-to-day accidents and other potentially hazardous industries. (U.K.)

  3. The risk

    International Nuclear Information System (INIS)

    Olin, N.; Delmestre, A.; Baumont, G.; El Jammal, M.H.; Brucker, G.; Mettendorf, M.; Kervern, G.Y.; Amalberti, R.; Digoin, A.; Lagrange, V.; Duval, D.; Setbon, M.; Godard, O.; Lagadec, P.; Heriard Dubreuil, G.; Miserey, Y.; Delalonde, J.C.; Solomarska, E.

    2006-01-01

    In this issue is studied the risk analysis in nuclear industry. The different chapters are the risk, its perception and its control; the measure of the perception of risks; misunderstanding, a limit for transparency policy. About the running systems on risk, the practical applications of research on the science of danger are detailed; human factors approaches, errors and risk is tackled and also human factors at the centre of safety progress by taking expert methods and transforming them into practical tools for managers; an example is given through the technological risks analysis rule in Total industrial group, or how harmonizing the methods to increase the performance; Some thoughts about the risks and its perception, the principle of precaution, the emergencies and breaking situations on the borderline of chaos; the civil society at the heart of the governance of activities generating risks; two stories, one is about the difficulties to get information, including about the passage of the cloud from Chernobyl, the second one is the account of an inhabitant of Chernobyl. (N.C.)

  4. Risk determination

    International Nuclear Information System (INIS)

    1993-01-01

    The issue gives a survey of the legal, theological, statistical and health aspects of risk determination. It includes the opinions of physicians, epidemiologists, mathematicians, toxicologists, biologists, theologists and physicists who explain and illustrate the term of risk from their perspective. (orig./DG) [de

  5. Risk management

    International Nuclear Information System (INIS)

    Magne, L.

    1999-01-01

    There is always a risk of an accident occurring at a nuclear power plant, however small. The problem lies in estimating the probability of it occurring. The method of probabilistic safety assessment provides this estimate, and by identifying the sources of potential risk, makes it possible to prevent them from occurring. It is not, however, a substitute for other decision-making processes. (author)

  6. Embracing risk

    Directory of Open Access Journals (Sweden)

    Ross Cagan

    2015-08-01

    Full Text Available I entered the science field because I imagined that scientists were society's “professional risk takers”, that they like surfing out on the edge. I understood that a lot of science – perhaps even most science – has to be a solid exploration of partly understood phenomena. But any science that confronts a difficult problem has to start with risk. Most people are at least a bit suspicious of risk, and scientists such as myself are no exception. Recently, risk-taking has been under attack financially, but this Editorial is not about that. I am writing about the long view and the messages we send to our trainees. I am Senior Associate Dean of the graduate school at Mount Sinai and have had the privilege to discuss these issues with the next generation of scientists, for whom I care very deeply. Are we preparing you to embrace risk?

  7. Nuclear risk

    International Nuclear Information System (INIS)

    Levenson, M.

    1989-01-01

    The title of our session, Nuclear Risk Versus Other Power Options, is provocative. It is also a title with different meanings to different people. To the utility chief executive officer, nuclear power is a high-risk financial undertaking because of political and economic barriers to cost recovery. To the utility dispatcher, it is a high-risk future power source since plant completion and start-up dates can be delayed for very long times due to uncertain legal and political issues. To the environmentalist, concerned about global effects such as greenhouse and acid rain, nuclear power is a relatively low risk energy source. To the financial people, nuclear power is a cash cow turned sour because of uncertainties as to what new plants will cost and whether they will even be allowed to operate. The statistics on risk are known and the results of probability risk assessment calculations of risks are known. The challenge is not to make nuclear power safer, it is already one of the safest, if not the safest, source of power currently available. The challenge is to find a way to communicate this to the public

  8. Risk theory

    CERN Document Server

    Schmidli, Hanspeter

    2017-01-01

    This book provides an overview of classical actuarial techniques, including material that is not readily accessible elsewhere such as the Ammeter risk model and the Markov-modulated risk model. Other topics covered include utility theory, credibility theory, claims reserving and ruin theory. The author treats both theoretical and practical aspects and also discusses links to Solvency II. Written by one of the leading experts in the field, these lecture notes serve as a valuable introduction to some of the most frequently used methods in non-life insurance. They will be of particular interest to graduate students, researchers and practitioners in insurance, finance and risk management.

  9. Risk factors.

    Science.gov (United States)

    Robbins, Catherine J; Connors, K C; Sheehan, Timothy J; Vaughan, James S

    2005-06-01

    Minimize surprises on your financial statement by adopting a model for integrated risk management that: Examines interrelationships among operations, investments, and financing. Incorporates concepts of the capital asset pricing model to manage unexpected volatility

  10. Risk Assessment

    Science.gov (United States)

    How the EPA conducts risk assessment to protect human health and the environment. Several assessments are included with the guidelines, models, databases, state-based RSL Tables, local contacts and framework documents used to perform these assessments.

  11. Technological risk

    Energy Technology Data Exchange (ETDEWEB)

    Dierkes, M; Coppock, R; Edwards, S

    1980-01-01

    The book begins with brief statements from representatives of political organizations. Part II presents an overview of the discussion about the control and management of technological progress. Parts III and IV discuss important elements in citizens' perception of technological risks and the development of consensus on how to deal with them. In Part V practical problems in the application of risk assessment and management, and in Part VI additional points are summarized.

  12. Risk Appetite

    OpenAIRE

    Berlinger, Edina; Váradi, Kata

    2015-01-01

    Our article firstly examines to what extent empirical research confirms the model of decision making based on a stable utility function. To this end, we have summarised the fundamental theoretical correlations relating to risk appetite, then went on to present the main results of behavioural research, with special focus on prospect theory, the correlations between socio-demographic and cognitive characteristics and risk propensity, as well as other influencing physical, mental and psychologic...

  13. Technological risk

    International Nuclear Information System (INIS)

    Dierkes, M.; Coppock, R.; Edwards, S.

    1980-01-01

    The book begins with brief statements from representatives of political organizations. Part II presents an overview of the discussion about the control and management of technological progress. Parts III and IV discuss important elements in citizens' perception of technological risks and the development of consensus on how to deal with them. In Part V practical problems in the application of risk assessment and management, and in Part VI additional points are summarized. (DG)

  14. Risk Assessment

    OpenAIRE

    Hrdová, Edita

    2012-01-01

    This diploma thesis is focused on companies risk evaluation before endorsement of Loan deriving from business relationships. The aim of this thesis is not only to describe individual steps of risk assessment, but also perfom analysis of particular companies based on available data, i.e. Balance sheet, Profit and Loss statement and external rating and after that propose solution for each company. My analysis will be based on theoretical knowledge, further on experience related to my job role a...

  15. Risk assessment

    DEFF Research Database (Denmark)

    Pedersen, Liselotte; Rasmussen, Kirsten; Elsass, Peter

    2010-01-01

    International research suggests that using formalized risk assessment methods may improve the predictive validity of professionals' predictions of risk of future violence. This study presents data on forensic psychiatric patients discharged from a forensic unit in Denmark in year 2001-2002 (n=107...... and the individual dynamic items strengthen the use of this scheme in clinical practice. (PsycINFO Database Record (c) 2010 APA, all rights reserved) (journal abstract)...

  16. Engineering risks

    International Nuclear Information System (INIS)

    Hauptmanns, U.; Werner, W.

    1991-01-01

    The book describes the methods of risk analysis and explains the procedures and results of a number of studies including the German Risk Study, Phase B and NUREG-1150. After defining basic concepts the methods of risk analysis are treated. In the field of nuclear energy studies for light water, fast breeder and high temperature reactors and for the nuclear fuel cycle are discussed; their relevant results are presented. Additionally, precursors to severe accidents are dealt with. Risk studies for process plants are described; their objectives and methods of analysis are examined. Furthermore, their approaches are compared with that of the German Risk Study, Phase A. Risk comparisons for nuclear, conventional and renewable energy sources are critically examined. Technical and legal aspects of the safety evaluation for nuclear power plants in the FRG and the potential of the combined use of the deterministic and probabilistic approaches are discussed. The book concludes with an overview of probabilistic safety goals in different countries. (orig.) With 52 figs

  17. The risks of measuring risk

    International Nuclear Information System (INIS)

    Berg, G.G.

    1982-01-01

    The author gives an overview of the Thirteenth Rochester International Conference on Environmental Toxicity, which examined both the logical soundness of the inference of risk and the validity of the environmental evidence of damage. Examples are itemized, concise introductions are given for each published paper in the proceedings, and an appropriate keynote is given by way of stating the established and alternate approach to risk measurement. The volume is described as ''more than a review of advance in measurement of risks to health . . . (but also) a landmark of a change in scientific opinion.''

  18. Risk communication

    International Nuclear Information System (INIS)

    Dombrowsky, Wolf R.; Kiel Univ.

    2009-01-01

    The study on risk communication identifies the deficiencies concerning empirical and theoretical knowledge on objective radiation hazards of the acting personnel (managers, politicians, jurists, etc.) in administrations, governmental agencies, and business management. This is especially problematic with respect to emergency planning and estimations concerning the public behavior. The incident/accident information in Germany is discussed based on the legislative regulations revealing the controversial perception between industry, legislative and public interest. Further topics include the meandering of the modern safety semantics and the public opinion concerning catastrophic risk.

  19. Minimizing risks

    International Nuclear Information System (INIS)

    Thompson, P.

    1991-01-01

    This article discusses ways to reduce the economic risk of independent energy projects. The topics of the article include risk categorization into areas of property, boiler and machinery, business income, and general liability, choosing a broker, choosing an insurer, and helping an insurer develop the best portfolio for the project. The author feels that attention to the guidelines for the right insurance coverage is as vital to a plant's economic stability as attention to the details of the blueprints is to its physical stability

  20. Risk analysis

    International Nuclear Information System (INIS)

    Baron, J.H.; Nunez McLeod, J.; Rivera, S.S.

    1997-01-01

    This book contains a selection of research works performed in the CEDIAC Institute (Cuyo National University) in the area of Risk Analysis, with specific orientations to the subjects of uncertainty and sensitivity studies, software reliability, severe accident modeling, etc. This volume presents important material for all those researches who want to have an insight in the risk analysis field, as a tool to solution several problems frequently found in the engineering and applied sciences field, as well as for the academic teachers who want to keep up to date, including the new developments and improvements continuously arising in this field [es

  1. Final report of fuel dynamics Test E7

    International Nuclear Information System (INIS)

    Doerner, R.C.; Murphy, W.F.; Stanford, G.S.; Froehle, P.H.

    1977-04-01

    Test data from an in-pile failure experiment of high-power LMFBR-type fuel pins in a simulated $3/s transient-overpower (TOP) accident are reported and analyzed. Major conclusions are that (1) a series of cladding ruptures during the 100-ms period preceding fuel release injected small bursts of fission gas into the flow stream; (2) gas release influenced subsequent cladding melting and fuel release [there were no measurable FCI's (fuel-coolant interactions), and all fuel motion observed by the hodoscope was very slow]; (3) the predominant postfailure fuel motion appears to be radial swelling that left a spongy fuel crust on the holder wall; (4) less than 4 to 6 percent of the fuel moved axially out of the original fuel zone, and most of this froze within a 10-cm region above the original top of the fuel zone to form the outlet blockage. An inlet blockage approximately 1 cm long was formed and consisted of large interconnected void regions. Both blockages began just beyond the ends of the fuel pellets

  2. Perceived Risk.

    Science.gov (United States)

    Ost, David H.

    1995-01-01

    Perceived risk is a function of information, knowledge, values, and perception. This exercise is designed to illustrate that in many situations there is no correct answer, only best-alternative choices. The exercise has five parts in which students work in groups of five. (LZ)

  3. Risk assessment and risk evaluation

    International Nuclear Information System (INIS)

    Niehaus, F.

    1978-01-01

    With the help of results of investigations and model calculations the risk of nuclear energy in routine operation is shown. In this context it is pointed out that the excellent operation results of reactors all over the world have led to the acceptability of risks from local loads no longer being in question. The attention of radiation protection is therefore focused on the emissions of long-living isotopes which collect in the atmosphere. With LWRs the risk of accidents is so minimal that statistical data is, and never will be available. One has to therefore fall back upon the so-called fault tree analyses. On the subject of risk evalution the author referred to a poll in Austria. From the result of this investigation one might conclude that nuclear energy serves as a crystallization point for a discussion of varying concepts for future development. More attention should be paid to this aspect from both sides, in order to objectify the further expansion of this source of energy. (orig./HP) [de

  4. Risk Marketing

    OpenAIRE

    Boutang , Jérôme; De Lara , Michel

    2016-01-01

    In a modern world increasingly perceived as uncertain, the mere purchase of a household cleaning product, or a seemingly harmless bottle of milk, conveys interrogations about potential hazards, from environmental to health impacts. The main purpose of this article is to suggest that risk could be considered as one of the major dimensions of choice for a wide range of concerns and markets, alongside aspiration/satisfaction, and tackled efficiently by mobilizing the recent findings of cognitive...

  5. Nuclear risk

    International Nuclear Information System (INIS)

    Mulkers, G.

    1988-01-01

    This file includes data on risks insured by the nuclear insurance pool in Belgium and on the Chernobyl accident covering injury, economic damage and compensation for the latter. Also included are the texts of the IAEA Conventions on Early Notification and on Assistance in Case of a Nuclear Accident as well as that of a Convention on long-distance transfrontier atmospheric pollution signed in Geneva [fr

  6. Risks of tobacco

    Science.gov (United States)

    Secondhand smoke - risks; Cigarette smoking - risks; Smoking and smokeless tobacco - risks; Nicotine - risks ... tobacco that are known to cause cancer. HEALTH RISKS OF SMOKING OR USING SMOKELESS TOBACCO Knowing the ...

  7. Heart disease - risk factors

    Science.gov (United States)

    Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...

  8. Infection and HLA-G Molecules in Nasal Polyposis

    Directory of Open Access Journals (Sweden)

    Roberta Rizzo

    2014-01-01

    Full Text Available Sinonasal polyposis (SNP is a chronic inflammatory pathology with an unclear aetiopathogenesis. Human papillomavirus (HPV infection is one candidate for the development of SNP for its epithelial cell trophism, hyperproliferative effect, and the induction of immune-modulatory molecules as HLA-G. We enrolled 10 patients with SNP without concomitant allergic diseases (SNP-WoAD, 10 patients with SNP and suffering from allergic diseases (SNP-WAD, and 10 control subjects who underwent rhinoplasty. We analyzed the presence of high- and low-risk HPV DNA and the expression of membrane HLA-G (mHLA-G and IL-10 receptor (IL-10R and of soluble HLA-G (sHLA-G and IL-10 by polyp epithelial cells. The results showed the presence of HPV-11 in 50% of SNP-WoAD patients (OR:5.5, all characterized by a relapsing disease. HPV-11 infection was absent in nonrelapsing SNP-WoAD patients, in SNP-WAD patients and in controls, supporting the hypothesis that HPV-11 increases risk of relapsing disease. HPV-11 positive SNP-WoAD patients presented with mHLA-G and IL-10R on epithelial cells from nasal polyps and showed secretion of sHLA-G and IL-10 in culture supernatants. No HLA-G expression was observed in HPV negative polyps. These data highlight new aspects of polyposis aetiopathogenesis and suggest HPV-11 and HLA-G/IL-10 presence as prognostic markers in the follow-up of SNP-WoAD.

  9. Verbal risk in communicating risk

    Energy Technology Data Exchange (ETDEWEB)

    Walters, J.C. [Northern Arizona Univ., Flagstaff, AZ (United States). School of Communication; Reno, H.W. [EG and G Idaho, Inc., Idaho Falls, ID (United States). Idaho National Engineering Lab.

    1993-03-01

    When persons in the waste management industry have a conversation concerning matters of the industry, thoughts being communicated are understood among those in the industry. However, when persons in waste management communicate with those outside the industry, communication may suffer simply because of poor practices such as the use of jargon, euphemisms, acronyms, abbreviations, language usage, not knowing audience, and public perception. This paper deals with ways the waste management industry can communicate risk to the public without obfuscating issues. The waste management industry should feel obligated to communicate certain meanings within specific contexts and, then, if the context changes, should not put forth a new, more appropriate meaning to the language already used. Communication of the waste management industry does not have to be provisional. The authors suggest verbal risks in communicating risk can be reduced significantly or eliminated by following a few basic communication principles. The authors make suggestions and give examples of ways to improve communication with the general public by avoiding or reducing jargon, euphemisms, and acronyms; knowing the audience; avoiding presumptive knowledge held by the audience; and understanding public perception of waste management issues.

  10. Risk perception

    International Nuclear Information System (INIS)

    Ahearne, J.F.

    1989-01-01

    Conflicts on technical issues frequently involve disagreements between the public and the technologists. This paper summarizes the major characteristics of three groups of technologists and four groups of the public which lead to many of the disagreements. To advance the mores of making decisions involving complex science or technology, technologists should develop an understanding of what information is needed for decisions, of the need for two-way communication with the public, and to become responsible for the accuracy and honesty of risk communication messages

  11. Publishing Risks

    Directory of Open Access Journals (Sweden)

    Mogens Steffensen

    2014-02-01

    Full Text Available “What is complicated is not necessarily insightful and what is insightful is not necessarily complicated: Risks welcomes simple manuscripts that contribute with insight, outlook, understanding and overview”—a quote from the first editorial of this journal [1]. Good articles are not characterized by their level of complication but by their level of imagination, innovation, and power of penetration. Creativity sessions and innovative tasks are most elegant and powerful when they are delicately simple. This is why the articles you most remember are not the complicated ones that you struggled to digest, but the simpler ones you enjoyed swallowing.

  12. Balancing Risk

    DEFF Research Database (Denmark)

    Nygaard, Lene; Rossen, Camilla Blach; Buus, Niels

    2015-01-01

    This study explored how eight pregnant women diagnosed with depression managed the decision whether or not to take antidepressants during pregnancy. In total, 11 interviews were conducted and analysed by means of constructivist grounded theory. The major category constructed was Balancing risk......, with two minor categories: Assessing depression and antidepressants and Evaluating the impact of significant others. The participants tried to make the safest decision, taking all aspects of their life into consideration. They described successful decision-making in the context of managing social norms...

  13. Proliferation risks

    International Nuclear Information System (INIS)

    Carchon, R.

    1998-09-01

    The report gives an overview of different aspects related to safeguards of fissile materials. Existing treaties including the Non-Proliferation Treaty, and the Tlatelolco and the Rarotonga Treaties are discussed. An overview of safeguards systems for the control of fissile materials as well as the role of various authorities is given. An overall overview of proliferation risks, the physical protection of fissile materials and the trade in fissile materials is given. Finally, the status in problem countries and de facto nuclear weapon states is discussed

  14. Risk Probabilities

    DEFF Research Database (Denmark)

    Rojas-Nandayapa, Leonardo

    Tail probabilities of sums of heavy-tailed random variables are of a major importance in various branches of Applied Probability, such as Risk Theory, Queueing Theory, Financial Management, and are subject to intense research nowadays. To understand their relevance one just needs to think...... analytic expression for the distribution function of a sum of random variables. The presence of heavy-tailed random variables complicates the problem even more. The objective of this dissertation is to provide better approximations by means of sharp asymptotic expressions and Monte Carlo estimators...

  15. Calculated risks

    International Nuclear Information System (INIS)

    Rodricks, J.V.

    1992-01-01

    This book is a clear, practical, and balanced view of toxicology and risk management. The introduction argues the case for risks assessment and outlines the benefits and problems associated with chemical exposure. The first part of the book covers the basic science and the sources of human exposure to chemicals. Absorption, distribution, metabolism, and excretion are covered in some detail. The subsequent chapter gives a lively discussion of toxicity studies and then describes slow and fast poisons. The author gives the arguments for as well as against animal testing. There is much public bewilderment caused by reports of cancer-causing pesticides in apple juice and poisons emanating from nearby hazardous waste sites. The author believes that too much has been written in an attempt to expose governmental and corporate ignorance, negligence, and corruption. This book is less of a polemic, and more of a clear, unbiased clarification of the scientific basis for our concerns and uncertainties. It should serve to refocus the debate

  16. Volcanic risk

    International Nuclear Information System (INIS)

    Rancon, J.P.; Baubron, J.C.

    1995-01-01

    This project follows the previous multi-disciplinary studies carried out by the French Bureau de Recherches Geologiques et Minieres (BRGM) on the two active volcanoes of the French lesser Antilles: Mt Pelee (Martinique) and Soufriere (Guadeloupe) for which geological maps and volcanic risk studies have been achieved. The research program comprises 5 parts: the study of pyroclastic deposits from recent eruptions of the two volcanoes for a better characterization of their eruptive phenomenology and a better definition of crisis scenarios; the study of deposits and structures of active volcanoes from Central America and the study of eruptive dynamics of andesite volcanoes for a transposition to Antilles' volcanoes; the starting of a methodological multi-disciplinary research (volcanology, geography, sociology...) on the volcanic risk analysis and on the management of a future crisis; and finally, the development of geochemical survey techniques (radon, CO 2 , H 2 O) on active volcanoes of Costa-Rica and Europe (Fournaise, Furnas, Etna) and their application to the Soufriere. (J.S.). 9 refs., 3 figs

  17. Challenges in Risk Assessment: Quantitative Risk Assessment

    OpenAIRE

    Jacxsens, Liesbeth; Uyttendaele, Mieke; De Meulenaer, Bruno

    2016-01-01

    The process of risk analysis consists out of three components, risk assessment, risk management and risk communication. These components are internationally well spread by Codex Alimentarius Commission as being the basis for setting science based standards, criteria on food safety hazards, e.g. setting maximum limits of mycotoxins in foodstuffs. However, the technical component risk assessment is hard to elaborate and to understand. Key in a risk assessment is the translation of biological or...

  18. Radiation risks and other risks

    International Nuclear Information System (INIS)

    Jansweyer, C.J.M.

    1981-01-01

    The differences in acceptance of risks of different nature (industrial, in the home, on the road, use of drugs, alcohol, tobacco, coffee or other food stuffs) by the public are compared on the basis of life expectancy values of different categories of people. The safety of radiologic work for both personnel and patients is considered in connection with the basic principles underlying the ICRP recommendations. A computation of the effective body dose equivalent for a mean medical X-ray examination and a nuclear in vivo examination is given. (Auth.)

  19. Biofilm Risks

    DEFF Research Database (Denmark)

    Wirtanen, Gun Linnea; Salo, Satu

    2016-01-01

    This chapter on biofilm risks deals with biofilm formation of pathogenic microbes, sampling and detection methods, biofilm removal, and prevention of biofilm formation. Several common pathogens produce sticky and/or slimy structures in which the cells are embedded, that is, biofilms, on various...... surfaces in food processing. Biofilms of common foodborne pathogens are reviewed. The issue of persistent and nonpersistent microbial contamination in food processing is also discussed. It has been shown that biofilms can be difficult to remove and can thus cause severe disinfection and cleaning problems...... in food factories. In the prevention of biofilm formation microbial control in process lines should both limit the number of microbes on surfaces and reduce microbial activity in the process. Thus the hygienic design of process equipment and process lines is important in improving the process hygiene...

  20. Managing risks

    International Nuclear Information System (INIS)

    Nathwani, J.S.

    1993-01-01

    The three principles to guide regulating authorities are: Risks shall be managed to maximize the total expected net benefit to society; The safety benefit to be promoted is quality-adjusted life expectancy; Decisions for the public in regard to health and safety must be open and apply across the entire range of hazards to life and health. Based on the principle that excessive spending on health and safety, or lack of necessary development, may cause poverty and thereby actually decrease (adjusted) life expectancy, the author has developed a Life Product Index which gives comparable results to the Human Development Index promoted by the United Nations Development Program. These two social indicators can be used for purposes such as project evaluation, choosing between alternative technologies, or evaluation of health and safety programs

  1. High risk human papillomavirus in the periodontium : A case control study

    Directory of Open Access Journals (Sweden)

    Anna Shipilova

    2017-01-01

    Full Text Available Background: Human papilloma viruses (HPVs are small DNA viruses that have been identified in periodontal pocket as well as gingival sulcus. High risk HPVs are also associated with a subset of head and neck carcinomas. It is thought that the periodontium could be a reservoir for HPV. Aims: 1. Detection of Human Papilloma virus (HPV in periodontal pocket as well as gingival of patients having localized chronic periodontitis and gingival sulcus of periodontally healthy subjects. 2. Quantitative estimation of E6 and E7 mRNA in subjects showing presence of HPV3. To assess whether periodontal pocket is a reservoir for HPV. Settings and Design: This case-control study included 30 subjects with localized chronic Periodontitis (cases and 30 periodontally healthy subjects (controls. Two samples were taken from cases, one from periodontal pocket and one from gingival sulcus and one sample was taken from controls. Methods and Materials: Samples were collected in the form of pocket scrapings and gingival sulcus scrapings from cases and controls respectively. These samples were sent in storage media for identification and estimation of E6/E7 mRNA of HPV using in situ hybridization and flow cytometry. Statistical analysis: Statistical analysis was done by using, mean, percentage and Chi Square test. A statistical package SPSS version 13.0 was used to analyze the data. P value < 0.05 was considered as statistically significant. Results: pocket samples as well as sulcus samples for both cases and controls were found to contain HPV E6/E7 mRNAInterpretation and Conclusion: Presence of HPV E6/E7 mRNA in periodontium supports the hypothesis that periodontal tissues serve as a reservoir for latent HPV and there may be a synergy between oral cancer, periodontitis and HPV. However prospective studies are required to further explore this link.

  2. Padronização de três ELISAs polivalentes com lipopolissacarídeos de cadeia longa dos sorotipos 1 e 5, 2, 3 e 7 ou 10 e 12 de Actinobacillus pleuropneumoniae Standardization of three polyvalent ELISA based on long chain lipopolysaccharides of serotypes 1 and 5, 2, 3 and 7, or 10 and 12 of Actinobacillus pleuropneumoniae

    Directory of Open Access Journals (Sweden)

    S.S. Kuchiishi

    2008-04-01

    Full Text Available Três ELISAs polivalentes baseados em lipopolissacarídeos de cadeia longa (LPS-CL foram estabelecidos para detectar anticorpos para todos os sorotipos prevalentes de Actinobacillus pleuropneumoniae. Foram testadas amostras provenientes do banco de soros de suínos experimentalmente inoculados com todos os sorotipos de A. pleuropneumoniae. Os ELISAs foram sensíveis à detecção de anticorpos contra todos os LPS-CL. Foram observadas reações cruzadas no ELISA polivalente produzido com os sorotipos 1 e 5, com anti-soros específicos para os sorotipos 9 e 11, pois os sorotipos 1, 9 e 11 apresentaram antígenos somáticos comuns. No polivalente com os sorotipos 2, 3 e 7, observaram-se reações com anti-soros dos sorotipos 4, 6 e 8, devido à presença de antígenos somáticos entre os sorotipos 3, 6 e 8 e entre os sorotipos 4 e 7. Amostras de soros de animais infectados com Mycoplasma hyopneumoniae, Mycoplasma flocculare e Haemophilus parasuis, agentes que acometem o sistema respiratório dos suínos, não apresentaram reações cruzadas com os antígenos baseados em LPS-CL.Three polyvalent ELISA based on long chain lipopolysaccharides (LC-LPS were established to detect all prevalent serotypes of Actinobacillus pleuropneumoniae. Samples from a serum bank of experimentally inoculated animals with all serotypes of A. pleuropneumoniae were tested. Antibodies specific to LC-LPS of each serotype were detected. Cross-reactions were observed in the polyvalent ELISA produced with serotypes 1 and 5, with specific antisera to serotypes 9 and 11 due to common somatic antigens presence in serotypes 1, 9, and 11. In the polyvalent with serotypes 2, 3 and 7 reactions were observed with antisera of serotypes 4, 6, and 8, due to the presence of somatic antigens in serotypes 3, 6, and 8 and serotypes 4 and 7. Experimentally infected animals with respiratory agents of swine Mycoplasma hyopneumoniae, Mycoplasma flocculare, and Haemophilus parasuis did not present

  3. NASA's Risk Management System

    Science.gov (United States)

    Perera, Jeevan S.

    2011-01-01

    Leadership is key to success. Phased-approach for implementation of risk management is necessary. Risk management system will be simple, accessible and promote communication of information to all relevant stakeholders for optimal resource allocation and risk mitigation. Risk management should be used by all team members to manage risks -- risk office personnel. Each group is assigned Risk Integrators who are facilitators for effective risk management. Risks will be managed at the lowest-level feasible, elevate only those risks that require coordination or management from above. Risk reporting and communication is an essential element of risk management and will combine both qualitative and quantitative elements. Risk informed decision making should be introduced to all levels of management. Provide necessary checks and balances to insure that risks are caught/identified and dealt with in a timely manner. Many supporting tools, processes & training must be deployed for effective risk management implementation. Process improvement must be included in the risk processes.

  4. Does radiation risk exist?

    International Nuclear Information System (INIS)

    Passchier, W.

    1996-01-01

    Risk assessment and risk management are parts of a dynamic process with the objective to decide on the tolerability of risk and on measures to keep risk within accepted limits. It enables all relevant parties to express their concerns and preferences regarding the different options for the human action involved and regarding the relative importance of criteria to decide on the tolerability of risk. Risk assessment has three phases; problem definition, risk analysis and risk characterization. Risk analysis is primarily a technical and scientific endeavour. With regard to problem definition and ride characterization consultation between risk assessors and risk managers (and other parties concerned) is a must. (author)

  5. Breast cancer risks and risk prediction models.

    Science.gov (United States)

    Engel, Christoph; Fischer, Christine

    2015-02-01

    BRCA1/2 mutation carriers have a considerably increased risk to develop breast and ovarian cancer. The personalized clinical management of carriers and other at-risk individuals depends on precise knowledge of the cancer risks. In this report, we give an overview of the present literature on empirical cancer risks, and we describe risk prediction models that are currently used for individual risk assessment in clinical practice. Cancer risks show large variability between studies. Breast cancer risks are at 40-87% for BRCA1 mutation carriers and 18-88% for BRCA2 mutation carriers. For ovarian cancer, the risk estimates are in the range of 22-65% for BRCA1 and 10-35% for BRCA2. The contralateral breast cancer risk is high (10-year risk after first cancer 27% for BRCA1 and 19% for BRCA2). Risk prediction models have been proposed to provide more individualized risk prediction, using additional knowledge on family history, mode of inheritance of major genes, and other genetic and non-genetic risk factors. User-friendly software tools have been developed that serve as basis for decision-making in family counseling units. In conclusion, further assessment of cancer risks and model validation is needed, ideally based on prospective cohort studies. To obtain such data, clinical management of carriers and other at-risk individuals should always be accompanied by standardized scientific documentation.

  6. Risk from environmental chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Somers, E [Environmental Health Directorate, Health Protection Branch, Health and Welfare Canada, Ontario

    1982-01-01

    The elements of risk assessment, namely risk identification, risk estimation, risk evaluation and risk management, are described with respect to the control of environmental chemicals. The methodology of risk estimation is outlined and examples given of its application to regulatory decision-making for a number of chemicals in Canada. Finally, the extent and limitations of the process of risk evaluation are considered together with the need to recognize the importance of the public's perception of the level of risk.

  7. Screening mammography. A risk versus risk decision

    International Nuclear Information System (INIS)

    Ritenour, E.R.; Hendee, W.R.

    1989-01-01

    The potential risk of a radiologic procedure often is compared with the potential benefit of the procedure. While risk vs. benefit analysis has been useful as a step toward increased communication and understanding among radiologists, referring physicians, and the general public, it has the disadvantage that risk and benefit are fundamentally different quantities. Hence, their juxtaposition for purposes of comparison presents contextual difficulties. In this article, the concept is presented of comparing the risk of doing a procedure with the risk of choosing not to do the procedure. An example of risk vs. risk analysis of screening mammography for women over the age of 50 is given, with the conclusion that the risk of having yearly mammograms is less than 1/10 the risk of early death caused by failure to diagnose breast cancer by x-ray mammography. This approach to risk analysis would yield interesting data for examinations that are part of more complicated diagnostic pathways.19 references

  8. Introduction to risk assessment

    International Nuclear Information System (INIS)

    Raina, V.M.

    2002-01-01

    This paper gives an introduction to risk assessment. It discusses the basic concepts of risk assessment, nuclear risk assessment process and products, the role of risk assessment products in nuclear safety assurance, the relationship between risk assessment and other safety analysis and risk assessment and safe operating envelope

  9. Absolute risk, absolute risk reduction and relative risk

    Directory of Open Access Journals (Sweden)

    Jose Andres Calvache

    2012-12-01

    Full Text Available This article illustrates the epidemiological concepts of absolute risk, absolute risk reduction and relative risk through a clinical example. In addition, it emphasizes the usefulness of these concepts in clinical practice, clinical research and health decision-making process.

  10. Enterprise risk management

    Energy Technology Data Exchange (ETDEWEB)

    Eaton, C. [Enbridge, Calgary, AB (Canada)

    2015-07-01

    Enterprise risk management (ERM) is a relative new, holistic and strategic approach for managing risks in modern organizations. ERM builds on and extends traditional risk management (RM). Risk is the effect of uncertainty on objectives - positive and/or negative. Risk management is a set of practices used to understand and address risk. ERM is a form of RM that emphasizes risk aggregation and integration. Risk aggregation is combining individual risks into categories ({sup r}olled up{sup )}. risk integration is embedding RM into organizational contexts ({sup b}uilt in{sup )}.

  11. NASA's Risk Management System

    Science.gov (United States)

    Perera, Jeevan S.

    2013-01-01

    Phased-approach for implementation of risk management is necessary. Risk management system will be simple, accessible and promote communication of information to all relevant stakeholders for optimal resource allocation and risk mitigation. Risk management should be used by all team members to manage risks - not just risk office personnel. Each group/department is assigned Risk Integrators who are facilitators for effective risk management. Risks will be managed at the lowest-level feasible, elevate only those risks that require coordination or management from above. Risk informed decision making should be introduced to all levels of management. ? Provide necessary checks and balances to insure that risks are caught/identified and dealt with in a timely manner. Many supporting tools, processes & training must be deployed for effective risk management implementation. Process improvement must be included in the risk processes.

  12. Risk and risk aversion in our society

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, B L [Pittsburgh Univ., PA (USA)

    1985-01-01

    The best way to understand the magnitude of a risk is to compare it with other risks with which we are familiar, and a convenient way of doing this is to compare risks on the basis of Loss of Life Expectancy, LLE, that they cause. The LLE due to various risks including energy generation is listed. The cost of programs to save lives by medical screening, highway safety and other methods is summarised. The public's perception of radiation risks is grossly exaggerated relative to other risks.

  13. Risk and risk aversion in our society

    International Nuclear Information System (INIS)

    Cohen, B.L.

    1985-01-01

    The best way to understand the magnitude of a risk is to compare it with other risks which we are familiar, and a convenient way of doing this is to compare risks on the basis of Loss of Life Expectancy, LLE, that they cause. The LLE due to various risks including energy generation is listed. The cost of programs to save lives by medical screening, highway safety and other methods is summarised. The public's perception of radiation risks is grossly exaggerated relative to other risks

  14. Downside Variance Risk Premium

    OpenAIRE

    Feunou, Bruno; Jahan-Parvar, Mohammad; Okou, Cedric

    2015-01-01

    We propose a new decomposition of the variance risk premium in terms of upside and downside variance risk premia. The difference between upside and downside variance risk premia is a measure of skewness risk premium. We establish that the downside variance risk premium is the main component of the variance risk premium, and that the skewness risk premium is a priced factor with significant prediction power for aggregate excess returns. Our empirical investigation highlights the positive and s...

  15. Risk control and the minimum significant risk

    International Nuclear Information System (INIS)

    Seiler, F.A.; Alvarez, J.L.

    1996-01-01

    Risk management implies that the risk manager can, by his actions, exercise at least a modicum of control over the risk in question. In the terminology of control theory, a management action is a control signal imposed as feedback on the system to bring about a desired change in the state of the system. In the terminology of risk management, an action is taken to bring a predicted risk to lower values. Even if it is assumed that the management action taken is 100% effective and that the projected risk reduction is infinitely well known, there is a lower limit to the desired effects that can be achieved. It is based on the fact that all risks, such as the incidence of cancer, exhibit a degree of variability due to a number of extraneous factors such as age at exposure, sex, location, and some lifestyle parameters such as smoking or the consumption of alcohol. If the control signal is much smaller than the variability of the risk, the signal is lost in the noise and control is lost. This defines a minimum controllable risk based on the variability of the risk over the population considered. This quantity is the counterpart of the minimum significant risk which is defined by the uncertainties of the risk model. Both the minimum controllable risk and the minimum significant risk are evaluated for radiation carcinogenesis and are shown to be of the same order of magnitude. For a realistic management action, the assumptions of perfectly effective action and perfect model prediction made above have to be dropped, resulting in an effective minimum controllable risk which is determined by both risk limits. Any action below that effective limit is futile, but it is also unethical due to the ethical requirement of doing more good than harm. Finally, some implications of the effective minimum controllable risk on the use of the ALARA principle and on the evaluation of remedial action goals are presented

  16. Risk and risk acceptance by society

    International Nuclear Information System (INIS)

    Statt, C.

    1977-01-01

    Various dimensions of risk are identified which relate to the manner in which risk is perceived and evaluated, and several self-consistent risk characteristics are explored. Factors which are thought to influence the perception of risk include the degree of personal control over the risk, the potential of episodic events, and the probable severity of injury if a risk event occurs. Risk-benefit analysis can be applied to three problems: the allocation of resources for safety expenditures, the setting of standards, and societal risk taking decisions. Calculations of benefit are needed for the third area of application, methods for the other two frequently do not require such a measure. (orig./RW) [de

  17. Modelos alternativos para detecção de locos de características quantitativas (QTL de carcaça e crescimento nos cromossomos 4, 5 e 7 de suínos Alternative models for detection of quantitative trait loci (QTL for growth and carcass traits in pigs chromosomes 4, 5 and 7

    Directory of Open Access Journals (Sweden)

    Tarcísio de Moraes Gonçalves

    2005-10-01

    Full Text Available O conhecimento do genoma pode auxiliar na identificação de regiões cromossômicas e, eventualmente, de genes que controlam características quantitativas (QTLs de importância econômica. Em um experimento com 1.129 suínos resultantes do cruzamento entre machos da raça Meishan e fêmeas Large White e Landrace, foram analisadas as características gordura intramuscular (GIM, em %, e ganho dos 25 aos 90 kg de peso vivo (GP, em g/dia, em 298 animais F1 e 831 F2, e espessura de toucinho (ET, em mm, em 324 F1 e 805 F2. Os animais das gerações F1 e F2 foram tipificados com 29 marcadores microsatélites. Estudou-se a ligação entre os cromossomos 4, 6 e 7 com GIM, ET e GP. Análises de QTL utilizando-se metodologia Bayesiana foram aplicadas mediante três modelos genéticos: modelo poligênico infinitesimal (MPI; modelo poligênico finito (MPF, considerando-se três locos; e MPF combinado com MPI. O número de QTLs, suas respectivas posições nos três cromossomos e o efeito fenotípico foram estimados simultaneamente. Os sumários dos parâmetros estimados foram baseados nas distribuições marginais a posteriori, obtidas por meio do uso da Cadeia de Markov, algoritmos de Monte Carlo (MCMC. Foi possível evidenciar dois QTLs relacionados a GIM nos cromossomos 4 e 6 e dois a ET nos cromossomos 4 e 7. Somente quando se ajustou o MPI, foram observados QTLs no cromossomo 4 para ET e GIM. Não foi possível detectar QTLs para a característica GP com a aplicação dessa metodologia, o que pode ter resultado do uso de marcadores não informativos ou da ausência de QTLs segregando nos cromossomos 4, 6 e 7 desta população. Foi evidenciada a vantagem de se analisar dados experimentais ajustando diferentes modelos genéticos; essas análises ilustram a utilidade e ampla aplicabilidade do método Bayesiano.Genome scans can be used to identify chromosomal regions and eventually genes that control quantitative traits (QTL of economic importance. In an

  18. Risk and reliability allocation to risk control

    International Nuclear Information System (INIS)

    Vojnovic, D.; Kozuh, M.

    1992-01-01

    The risk allocation procedure is used as an analytical model to support the optimal decision making for reliability/availability improvement planning. Both levels of decision criteria, the plant risk measures and plant performance indices, are used in risk allocation procedure. Decision support system uses the multi objective decision making concept. (author) [sl

  19. Risk Factors for Scleroderma

    Science.gov (United States)

    ... You are here: Home For Patients Risk Factors Risk Factors for Scleroderma The cause of scleroderma is ... what biological factors contribute to scleroderma pathogenesis. Genetic Risk Scleroderma does not tend to run in families ...

  20. Risk Factors and Prevention

    Science.gov (United States)

    ... Resources Risk Factors & Prevention Back to Patient Resources Risk Factors & Prevention Even people who look healthy and ... Blood Pressure , high cholesterol, diabetes, and thyroid disease. Risk Factors For Arrhythmias and Heart Disease The following ...

  1. Hepatitis Risk Assessment

    Science.gov (United States)

    ... please visit this page: About CDC.gov . Hepatitis Risk Assessment Recommend on Facebook Tweet Share Compartir Viral Hepatitis. Are you at risk? Take this 5 minute Hepatitis Risk Assessment developed ...

  2. Risk communication and environmental risk assessment

    International Nuclear Information System (INIS)

    Petts, J.

    1994-01-01

    This paper attempts to provide a broad context for consideration of appropriate risk communication approaches. It examines the basis of public concerns and in particular the non-risk dimensions. The latter are so important in any risk decision that means of communication which can deal with them are required which extend beyond understanding how to present risk estimates. These means relate to (a) the decision processes themselves and the extent to which they provide for involvement of the public in decisions, (b) the communication skills of experts, and (c) the robustness of the risk information which is available. (Author)

  3. Methods of risk assessment

    International Nuclear Information System (INIS)

    Jones, D.R.

    1981-01-01

    The subject is discussed under the headings: introduction (identification, quantification of risk); some approaches to risk evaluation (use of the 'no risk' principle; the 'acceptable risk' method; risk balancing; comparison of risks, benefits and other costs); cost benefit analysis; an alternative approach (tabulation and display; description and reduction of the data table); identification of potential decision sets consistent with the constraints. Some references are made to nuclear power. (U.K.)

  4. Information security risk analysis

    CERN Document Server

    Peltier, Thomas R

    2001-01-01

    Effective Risk AnalysisQualitative Risk AnalysisValue AnalysisOther Qualitative MethodsFacilitated Risk Analysis Process (FRAP)Other Uses of Qualitative Risk AnalysisCase StudyAppendix A: QuestionnaireAppendix B: Facilitated Risk Analysis Process FormsAppendix C: Business Impact Analysis FormsAppendix D: Sample of ReportAppendix E: Threat DefinitionsAppendix F: Other Risk Analysis OpinionsIndex

  5. Foundations of Risk Analysis

    CERN Document Server

    Aven, Terje

    2012-01-01

    Foundations of Risk Analysis presents the issues core to risk analysis - understanding what risk means, expressing risk, building risk models, addressing uncertainty, and applying probability models to real problems. The author provides the readers with the knowledge and basic thinking they require to successfully manage risk and uncertainty to support decision making. This updated edition reflects recent developments on risk and uncertainty concepts, representations and treatment. New material in Foundations of Risk Analysis includes:An up to date presentation of how to understand, define and

  6. Assessment of cardiovascular risk.

    LENUS (Irish Health Repository)

    Cooney, Marie Therese

    2010-10-01

    Atherosclerotic cardiovascular disease (CVD) is the most common cause of death worldwide. Usually atherosclerosis is caused by the combined effects of multiple risk factors. For this reason, most guidelines on the prevention of CVD stress the assessment of total CVD risk. The most intensive risk factor modification can then be directed towards the individuals who will derive the greatest benefit. To assist the clinician in calculating the effects of these multiple interacting risk factors, a number of risk estimation systems have been developed. This review address several issues regarding total CVD risk assessment: Why should total CVD risk be assessed? What risk estimation systems are available? How well do these systems estimate risk? What are the advantages and disadvantages of the current systems? What are the current limitations of risk estimation systems and how can they be resolved? What new developments have occurred in CVD risk estimation?

  7. On portfolio risk diversification

    Science.gov (United States)

    Takada, Hellinton H.; Stern, Julio M.

    2017-06-01

    The first portfolio risk diversification strategy was put into practice by the All Weather fund in 1996. The idea of risk diversification is related to the risk contribution of each available asset class or investment factor to the total portfolio risk. The maximum diversification or the risk parity allocation is achieved when the set of risk contributions is given by a uniform distribution. Meucci (2009) introduced the maximization of the Rényi entropy as part of a leverage constrained optimization problem to achieve such diversified risk contributions when dealing with uncorrelated investment factors. A generalization of the risk parity is the risk budgeting when there is a prior for the distribution of the risk contributions. Our contribution is the generalization of the existent optimization frameworks to be able to solve the risk budgeting problem. In addition, our framework does not possess any leverage constraint.

  8. VALUE AT RISK - CORPORATE RISK MEASUREMENT

    Directory of Open Access Journals (Sweden)

    Anis Cecilia-Nicoleta

    2011-12-01

    Full Text Available The notion of 'risk' is used in a number of sciences. The Faculty of Law studies the risk depending on its legality. The Accident Theory applies this term to describe the damage and the disasters. One can find studies on the risks in the works of psychology, philosophy, medicine and within each of these areas the study of the risk is based on the given science subject and, of course, on their methods and approaches. Such a variety of risk study is explained by the diversity of this phenomenon. Under the market economy conditions, the risk is an essential component of any economic agent management policy, of the approach developed by this one, a strategy that depends almost entirely on individual ability and capacity to anticipate his evolution and to exploit his opportunities, assuming a so-called 'risk of business failure.' There are several ways to measure the risks in projects, one of the most used methods to measure this being the Value at Risk(VaR. Value at Risk (VaR was made famous by JP Morgan in the mid 1990s, by introducing the RiskMetrics approach, and hence, by far, has been sanctioned by several Governing Bodies throughout the world bank. In short, it measures the value of risk capital stocks in a given period at a certain probability of loss. This measurement can be modified for risk applications through, for example, the potential loss values affirmation in a certain amount of time during the economic life of the project- clearly, a project with a lower VaR is better. It should be noted that it is not always possible or advisable for a company to limit itself to the remote analysis of each risk because the risks and their effects are interdependent and constitute a system .In addition, there are risks which, in combination with other risks, tend to produce effects which they would not have caused by themselves and risks that tend to offset and even cancel each other out.

  9. Environmental Risk Communication through Qualitative Risk Assessment

    Directory of Open Access Journals (Sweden)

    Sabre J. Coleman

    2014-06-01

    Full Text Available Environmental analysts are often hampered in communicating the risks of environmental contaminants due to the myriad of regulatory requirements that are applicable. The use of a qualitative, risk-based control banding strategy for assessment and control of potential environmental contaminants provides a standardized approach to improve risk communication. Presented is a model that provides an effective means for determining standardized responses and controls for common environmental issues based on the level of risk. The model is designed for integration within an occupational health and safety management system to provide a multidisciplinary environmental and occupational risk management approach. This environmental model, which utilizes multidisciplinary control banding strategies for delineating risk, complements the existing Risk Level Based Management System, a proven method in a highly regulated facility for occupational health and safety. A simplified environmental risk matrix is presented that is stratified over four risk levels. Examples of qualitative environmental control banding strategies are presented as they apply to United States regulations for construction, research activities, facility maintenance, and spill remediation that affect air, water, soil, and waste disposal. This approach offers a standardized risk communication language for multidisciplinary issues that will improve communications within and between environmental health and safety professionals, workers, and management.

  10. Dutch Risk Assessment tools

    NARCIS (Netherlands)

    Venema, A.

    2015-01-01

    The ‘Risico- Inventarisatie- en Evaluatie-instrumenten’ is the name for the Dutch risk assessment (RA) tools. A RA tool can be used to perform a risk assessment including an evaluation of the identified risks. These tools were among the first online risk assessment tools developed in Europe. The

  11. Identifying and Managing Risk.

    Science.gov (United States)

    Abraham, Janice M.

    1999-01-01

    The role of the college or university chief financial officer in institutional risk management is (1) to identify risk (physical, casualty, fiscal, business, reputational, workplace safety, legal liability, employment practices, general liability), (2) to develop a campus plan to reduce and control risk, (3) to transfer risk, and (4) to track and…

  12. Strategic Risk Assessment

    Science.gov (United States)

    Derleth, Jason; Lobia, Marcus

    2009-01-01

    This slide presentation provides an overview of the attempt to develop and demonstrate a methodology for the comparative assessment of risks across the entire portfolio of NASA projects and assets. It includes information about strategic risk identification, normalizing strategic risks, calculation of relative risk score, and implementation options.

  13. Risk management and safety

    International Nuclear Information System (INIS)

    Niehaus, F.; Novegno, A.

    1985-01-01

    Risk assessment, including probabilistic analyses, has made great progress over the past decade. In spite of the inherent uncertainties it has now become possible to utilize methods and results for decision making at various levels. This paper will, therefore, review risk management in industrial installations, risk management for energy safety policy and prospects of risk management in highly industrialized areas. (orig.) [de

  14. Man, technology and risk

    Energy Technology Data Exchange (ETDEWEB)

    Renn, O

    1981-06-01

    Using the instruments of empirical social sciences, a cross-section study was conducted comprising experiments on qualitative risk characteristics, in-depth interviews on mechanisms of risk perception and representative surveys of the public on technical risk sources, in particular with regard to nuclear energy. The results of these studies show that person-related expectations in respect of risk consequences, the possibility of personal influencing control, the severeness of risk consequences and one's own risk propensity play a significant role in the evaluation of risks. (Translated from German, original report Juel-Spez--67).

  15. Catalog of risks

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, B L; Lee, I S [Pittsburgh Univ., PA (USA). Dept. of Physics

    1979-06-01

    Information on risks is collected from various sources and converted into loss of life expectancy throughout life and in various age ranges. Risks included are radiation, accidents of various types, various diseases, overweight, tobacco use, alcohol and drugs, coffee, saccharin, and The Pill, occupational risks, socioeconomic factors, marital status, geography, serving in U.S. armed forces in Vietnam, catastrophic events, energy production, and technology in general. Information is also included on methods for reducing risks, risks in individual actions, very-hazardous activities, and priorities and perspective. Risks of natural and occupational radiation and exposure to radioactivity from the nuclear industry are compared with risks of similar or competing activities.

  16. A catalog of risks

    International Nuclear Information System (INIS)

    Cohen, B.L.; Lee, I.S.

    1979-01-01

    Information on risks is collected from various sources and converted into loss of life expectancy throughout life and in various age ranges. Risks included are radiation, accidents of various types, various diseases, overweight, tobacco use, alcohol and drugs, coffee, saccharin, and The Pill, occupational risks, socioeconomic factors, marital status, geography, serving in U.S. armed forces in Vietnam, catastrophic events, energy production, and technology in general. Information is also included on methods for reducing risks, risks in individual actions, very-hazardous activities, and priorities and perspective. Risks of natural and occupational radiation and exposure to radioactivity from the nuclear industry are compared with risks of similar or competing activities. (author)

  17. Rethinking risk management

    International Nuclear Information System (INIS)

    Kloman, H.F.

    1992-01-01

    The purpose of this paper is to bring together the ideas of those who currently practice the many different forms of risk management on a global basis. These forms include guidance of public policy on macro risks, risk financing and insurance for many larger commercial organizations, managing credit, currency and interest rate risks for financial institutions, plus other extensions of risk management including security, quality control, and quality assurance in a health-care environment

  18. A background of risks

    International Nuclear Information System (INIS)

    Griffiths, R.F.

    1981-01-01

    The subject is reviewed under the headings: introduction (historical and general description of harm, hazards and risk and attempts to define them); expressions of risk (individual risk; fatal accident frequency rate; expressions of risk in terms of deaths suffered per unit of activity; loss of life expectancy; frequency vs consequence lines); comparability of risks. The examples include some references to radiation hazards and reactor accidents. (U.K.)

  19. Probabilistic risk analysis and terrorism risk.

    Science.gov (United States)

    Ezell, Barry Charles; Bennett, Steven P; von Winterfeldt, Detlof; Sokolowski, John; Collins, Andrew J

    2010-04-01

    Since the terrorist attacks of September 11, 2001, and the subsequent establishment of the U.S. Department of Homeland Security (DHS), considerable efforts have been made to estimate the risks of terrorism and the cost effectiveness of security policies to reduce these risks. DHS, industry, and the academic risk analysis communities have all invested heavily in the development of tools and approaches that can assist decisionmakers in effectively allocating limited resources across the vast array of potential investments that could mitigate risks from terrorism and other threats to the homeland. Decisionmakers demand models, analyses, and decision support that are useful for this task and based on the state of the art. Since terrorism risk analysis is new, no single method is likely to meet this challenge. In this article we explore a number of existing and potential approaches for terrorism risk analysis, focusing particularly on recent discussions regarding the applicability of probabilistic and decision analytic approaches to bioterrorism risks and the Bioterrorism Risk Assessment methodology used by the DHS and criticized by the National Academies and others.

  20. Risk assessment and risk management of mycotoxins.

    Science.gov (United States)

    2012-01-01

    Risk assessment is the process of quantifying the magnitude and exposure, or probability, of a harmful effect to individuals or populations from certain agents or activities. Here, we summarize the four steps of risk assessment: hazard identification, dose-response assessment, exposure assessment, and risk characterization. Risk assessments using these principles have been conducted on the major mycotoxins (aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, and zearalenone) by various regulatory agencies for the purpose of setting food safety guidelines. We critically evaluate the impact of these risk assessment parameters on the estimated global burden of the associated diseases as well as the impact of regulatory measures on food supply and international trade. Apart from the well-established risk posed by aflatoxins, many uncertainties still exist about risk assessments for the other major mycotoxins, often reflecting a lack of epidemiological data. Differences exist in the risk management strategies and in the ways different governments impose regulations and technologies to reduce levels of mycotoxins in the food-chain. Regulatory measures have very little impact on remote rural and subsistence farming communities in developing countries, in contrast to developed countries, where regulations are strictly enforced to reduce and/or remove mycotoxin contamination. However, in the absence of the relevant technologies or the necessary infrastructure, we highlight simple intervention practices to reduce mycotoxin contamination in the field and/or prevent mycotoxin formation during storage.

  1. Risk assessment terminology: risk communication part 1

    Directory of Open Access Journals (Sweden)

    Gaetano Liuzzo

    2016-03-01

    Full Text Available The paper describes the terminology of risk communication in the view of food safety: the theory of stakeholders, the citizens’ involvement and the community interest and consultation are reported. Different aspects of risk communication (public communication, scientific uncertainty, trust, care, consensus and crisis communication are discussed.

  2. Risk perception versus seismic risk: An introduction

    International Nuclear Information System (INIS)

    Cubeddu, Francesca

    2015-01-01

    A seismic event generally has consequences on the social relationships, economy and culture of the impacted territory. As Mary Douglas quotes, a change into the social perception of risk as consequence of an earthquake may have effects on the lifestyle of the local community. The above mentioned statement is the starting point of this article. illustrating the difference between peril and risk is the second point. According to the Aristotelian theory of categories, risk can be considered as a human characteristic depending on social and cultural factors. Risk is here intended as a social category and cannot be de facto reported as a statistical or stochastic function based on a mathematical formula, as long assumed in the past. This approach, then, requires a deep revision. In this sense, and following the concept of risk perception, seismic risk is analysed in this article in terms of impacts, precautionary measures, risk assessment and management. Knowledge of this topic cannot be intended as a simple philosophical exercise, since right on awareness depend risk reduction, humans and goods too [it

  3. Exploration Health Risks: Probabilistic Risk Assessment

    Science.gov (United States)

    Rhatigan, Jennifer; Charles, John; Hayes, Judith; Wren, Kiley

    2006-01-01

    Maintenance of human health on long-duration exploration missions is a primary challenge to mission designers. Indeed, human health risks are currently the largest risk contributors to the risks of evacuation or loss of the crew on long-duration International Space Station missions. We describe a quantitative assessment of the relative probabilities of occurrence of the individual risks to human safety and efficiency during space flight to augment qualitative assessments used in this field to date. Quantitative probabilistic risk assessments will allow program managers to focus resources on those human health risks most likely to occur with undesirable consequences. Truly quantitative assessments are common, even expected, in the engineering and actuarial spheres, but that capability is just emerging in some arenas of life sciences research, such as identifying and minimize the hazards to astronauts during future space exploration missions. Our expectation is that these results can be used to inform NASA mission design trade studies in the near future with the objective of preventing the higher among the human health risks. We identify and discuss statistical techniques to provide this risk quantification based on relevant sets of astronaut biomedical data from short and long duration space flights as well as relevant analog populations. We outline critical assumptions made in the calculations and discuss the rationale for these. Our efforts to date have focussed on quantifying the probabilities of medical risks that are qualitatively perceived as relatively high risks of radiation sickness, cardiac dysrhythmias, medically significant renal stone formation due to increased calcium mobilization, decompression sickness as a result of EVA (extravehicular activity), and bone fracture due to loss of bone mineral density. We present these quantitative probabilities in order-of-magnitude comparison format so that relative risk can be gauged. We address the effects of

  4. Risk perception and credibility of risk communication

    Energy Technology Data Exchange (ETDEWEB)

    Sjoeberg, L

    1992-10-01

    Experts and the public frequently disagree when it comes to risk assessment. The reasons for such disagreement are discussed, and it is pointed out that disagreement among experts and lack of full understanding of real risks contributes to skepticism among the public. The notion that people are in general reacting in a highly emotional and non-rational, phobic, manner is rejected. The very conditions for risk assessment present to the public, and common-sense cognitive dynamics, are better explanations of risk perception, as are some social psychological concepts. If trust is to be established in a country where it is quite low some kind of politically regulated public influence on decision making and risk monitoring is probably needed, e.g. by means of a publicly elected and responsible ombudsman. 57 refs, 8 figs, 5 tabs.

  5. Risk perception and credibility of risk communication

    International Nuclear Information System (INIS)

    Sjoeberg, L.

    1992-10-01

    Experts and the public frequently disagree when it comes to risk assessment. The reasons for such disagreement are discussed, and it is pointed out that disagreement among experts and lack of full understanding of real risks contributes to skepticism among the public. The notion that people are in general reacting in a highly emotional and non-rational, phobic, manner is rejected. The very conditions for risk assessment present to the public, and common-sense cognitive dynamics, are better explanations of risk perception, as are some social psychological concepts. If trust is to be established in a country where it is quite low some kind of politically regulated public influence on decision making and risk monitoring is probably needed, e.g. by means of a publicly elected and responsible ombudsman. 57 refs, 8 figs, 5 tabs

  6. Preferences over Social Risk

    DEFF Research Database (Denmark)

    Harrison, Glenn W.; Lau, Morten; Rutström, E. Elisabet

    2013-01-01

    that subjects systematically reveal different risk attitudes in a social setting with no prior knowledge about the risk preferences of others compared to when they solely bear the consequences of the decision. However, we also find that subjects are significantly more risk averse when they know the risk......We elicit individual preferences over social risk. We identify the extent to which these preferences are correlated with preferences over individual risk and the well-being of others. We examine these preferences in the context of laboratory experiments over small, anonymous groups, although...... the methodological issues extend to larger groups that form endogenously (e.g., families, committees, communities). Preferences over social risk can be closely approximated by individual risk attitudes when subjects have no information about the risk preferences of other group members. We find no evidence...

  7. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky......We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...

  8. Diversity in Risk Communication

    Directory of Open Access Journals (Sweden)

    Agung Nur Probohudono

    2013-03-01

    Full Text Available This study analyses the communication of the five major categories of risk (business, strategy, market and credit risk disclosure over the volatile 2007-2009 Global Financial Crisis (GFC time period in key South East Asian countries’ manufacturing listed companies. This study is important as it contributes to the literature by providing insights into the voluntary risk disclosure practices using sample countries with different economic scenarios. Key findings are that business risk is the most disclosed category and strategy risk is the least disclosed. Business and credit risk disclosure consistently increase over the three year period, while operating, market and strategy risk disclosure increase in 2008, but then decrease slightly in 2009. Statistical analysis reveals that country of incorporation and size help predict risk disclosure levels. The overall low disclosure levels (26-29% highlight the potential for far higher communication of key risk factors.

  9. Risk, Resources and Structures

    DEFF Research Database (Denmark)

    Lyng Jensen, Jesper; Ponsaing, Claus Due; Thrane, Sof

    2012-01-01

    In this article, we describe a basic mechanism by which risk events can induce indirect value losses to the risk owner: a value loss arising from a risk event interfering with activities that have no logical connection with the risk event other than that of having the same owner; a mechanism we...... to large risk events is to mitigate the consequences of the risk event through negotiating with the environment. If such negotiations fail, the subject will have no alternative but to let other activities and projects under direct control of the risk owner suffer. We end the article with conjectures....... The risk cost component presented in this article, whose existence has previously been argued in the risk literature, has been documented in a single factorial experiment with a unique simulation device named Risky Business. Through our experiments, we have shown that the first response of subjects exposed...

  10. Risk management overview

    International Nuclear Information System (INIS)

    McGovern, S.

    1995-01-01

    Launching of the first natural gas contract by the New York Mercantile Exchange (NYMEX) in April 1990 was a huge success which allowed natural gas to surpass crude oil as the most successful launch of any commodity contract. Despite this unprecedented initial success it must be kept in mind that in a competitive marketplace there are risks of many kinds (market risks, price risks, basis risks, currency risks and timing risks), that parties must deal with in everyday operations. The concept of risk management was defined, techniques and issues in risk management were explained, a glossary of fully explained industry terms, and basic financial tools most often used in risk management, were provided. 11 figs

  11. Fracture Risk and Risk Factors for Osteoporosis.

    Science.gov (United States)

    Schürer, Christian; Wallaschofski, Henri; Nauck, Matthias; Völzke, Henry; Schober, Hans-Christof; Hannemann, Anke

    2015-05-25

    As the population ages, diseases of the elderly are becoming more common, including osteoporosis. Ways to assess the risk of fracture and the distribution and effects of known risk factors for osteoporosis will be important in planning for future healthcare needs, as well as in the development of preventive strategies. The study population included 6029 men and women aged 20-90 who underwent examination in the second follow-up wave of the Study of Health in Pomerania (SHIP-2) or in the basal SHIP-Trend Study. The risk of fracture was estimated on the basis of quantitative ultrasonography of the calcaneus. Prior fractures and risk factors for osteoporosis were ascertained in standardized interviews. 4.6% of the male subjects and 10.6% of the female subjects were judged to have an elevated risk of fracture. The corresponding percentages among subjects over age 65 were 8.8% for men and 28.2% for women. Even among subjects under age 55, risk factors for osteoporosis were associated with lower bone stiffness: the mean stiffness index was 103/98 (men/women) without risk factors, 99/96 with one risk factor, and 93/95 with more than one risk factor. Logistic regression analysis yielded an odds ratio of 1.89 (95% confidence interval: 1.44-2.50; p<0.01) for prevalent fractures among subjects aged 75 and older compared to subjects under age 55. The data indicate a high prevalence of osteoporosis from age 65 onward. These findings are consistent with those of other studies from Germany and across Europe. Younger men and women should already begin taking steps to counteract modifiable risk factors.

  12. Observations on risk analysis

    International Nuclear Information System (INIS)

    Thompson, W.A. Jr.

    1979-11-01

    This paper briefly describes WASH 1400 and the Lewis report. It attempts to define basic concepts such as risk and risk analysis, common mode failure, and rare event. Several probabilistic models which go beyond the WASH 1400 methodology are introduced; the common characteristic of these models is that they recognize explicitly that risk analysis is time dependent whereas WASH 1400 takes a per demand failure rate approach which obscures the important fact that accidents are time related. Further, the presentation of a realistic risk analysis should recognize that there are various risks which compete with one another for the lives of the individuals at risk. A way of doing this is suggested

  13. Project Risk Management

    Science.gov (United States)

    Jr., R. F. Miles

    1995-01-01

    Project risk management is primarily concerned with performance, reliability, cost, and schedule. Environmental risk management is primarily concerned with human health and ecological hazards and likelihoods. This paper discusses project risk management and compares it to environmental risk management, both with respect to goals and implementation. The approach of the Jet Propulsion Laboratory to risk management is presented as an example of a project risk management approach that is an extension to NASA NHB 7120.5: Management of Major System Programs and Projects.

  14. Risk, Uncertainty, and Entrepreneurship

    DEFF Research Database (Denmark)

    Koudstaal, Martin; Sloof, Randolph; Van Praag, Mirjam

    2016-01-01

    21288). The results indicate that entrepreneurs perceive themselves as less risk averse than managers and employees, in line with common wisdom. However, when using experimental incentivized measures, the differences are subtler. Entrepreneurs are only found to be unique in their lower degree of loss...... aversion, and not in their risk or ambiguity aversion. This combination of results might be explained by our finding that perceived risk attitude is not only correlated to risk aversion but also to loss aversion. Overall, we therefore suggest using a broader definition of risk that captures this unique...... feature of entrepreneurs: their willingness to risk losses....

  15. Risk, Uncertainty and Entrepreneurship

    DEFF Research Database (Denmark)

    Koudstaal, Martin; Sloof, Randolph; Van Praag, Mirjam

    . Entrepreneurs are only found to be unique in their lower degree of loss aversion, and not in their risk or ambiguity aversion. This combination of results might be explained by our finding that perceived risk attitude is not only correlated to risk aversion but also to loss aversion. Overall, we therefore...... entrepreneurs to managers – a suitable comparison group – and employees (n = 2288). The results indicate that entrepreneurs perceive themselves as less risk averse than managers and employees, in line with common wisdom. However, when using experimental incentivized measures, the differences are subtler...... suggest using a broader definition of risk that captures this unique feature of entrepreneurs; their willingness to risk losses....

  16. Gender, risk and journalism

    OpenAIRE

    Harris, Janet; Mosdell, Nicholas; Griffiths, James

    2016-01-01

    Are female journalists more at risk in covering conflict than their male colleagues? \\ud Beck states ‘risk is the anticipation of the catastrophe – so it is existent and non-existent’. Is the contention that female journalists are more at risk, knowledge, or a construction of knowledge? Are Editors and journalists who decide that women are more at risk merely anticipating a catastrophe? There is no certainty that women would be more at risk, but the fear that women are more at risk can preven...

  17. Cyber risk in banking

    OpenAIRE

    Linert, Jan

    2015-01-01

    The bachelor thesis deals with the cyber risk in banking industry. Its main goal is to stress the imporatance of cyber risk both verbally and numericaly and review the approach of banks to this risk. The first part of this thesis specifies what cyber risk is and how it fits among other operational risks, presents the common cyber-attacks and archetypes of cyber criminals, later it delves into the cyber risk in Czech Republic and at the end of this part it mentions the legislation that covers ...

  18. Risk management and energy systems

    International Nuclear Information System (INIS)

    Carlevaro, F.; Romerio, F.

    1992-01-01

    In five sessions the following topics were dealt with: risk problems, risk analysis and evaluation tools, risks in industrial societies, risks of energy production, technological risks, ethics and political-social consensus. figs., tabs., refs

  19. Risk and society

    International Nuclear Information System (INIS)

    Tubiana, M.; Vrousos, C.; Pages, J.P.; Carde, C.

    1999-01-01

    This book brings together the communications presented at the colloquium 'risk and society' held in Paris (France) on November 1998. During this colloquium, the various aspects of risk and of its management were discussed by medical specialists, historians, industrialists, engineers, philosophers, lawyers, politicians and administration representatives. The first theme concerns the controversies generated by the development of some activities (genetics, bio-technologies, nuclear and radiations use). The second theme concerns the management of risks and the way to conciliate the point of view of authorities and citizens (confidence of the public with respect to experts, scientists, industrialists, government and administrative representatives, role played by the media). The debates that took place during the colloquium have shown that the public opinion concerning the nuclear activities or the new technologies greatly depends on the ideological attitudes and on the public's likes and dislikes with respect to some categories of actors (distrust with respect to public decisions, fears with respect to changes and future, nostalgia of the past). The following aspects are reviewed: Notions of risk and hazard (risk and health, risk in today's society, medicine and society, the point of view of the industrialists and of the scientific and technical specialists); from the psychological aspects of the risk to its social aspects (survey of the risk assessment battlefield, social attenuation and amplification of risk, the feeling of risks in Europe, insecurity and delinquency, controversies around radioactivity and health); the negotiation and communication about risks (risk and public health, negotiation around risks, risks and information dissemination about the public debate, communication and crisis, evolution of risk communication, comparison between American and European approaches, the Seveso directive); the public debate and the evolution of risks management (the

  20. Risk management guide

    International Nuclear Information System (INIS)

    Briscoe, G.J.

    1977-06-01

    Risk management requires an assessment or a knowledge of risk. This, in turn, requires identification of hazards (sources of risk) and a determination of risk (evaluation of the hazard degree). The hazard identification and risk analysis techniques presented in this Guide are, in general, based on the MORT concept that accidents result from unwanted energy flow in the absence of adequate controls and/or barriers. This Guide presents an analytical tree designed to prevent oversight of specific energy sources in risk identification. Hazard identification by field personnel is also discussed. Quantitative risk analysis is discussed in the following section. A method for summary of the risks for each energy classification is given. This method uses a graphical log-normal projection so that low probability events, which are not adequately represented in the experience data, are included in the risk assessment. This permits a more acceptable risk assessment since catastrophes are not ignored, even though the actual risk is only approximated. In addition, a few examples of risk analysis of specific hazards are given. Rudimentary probability and fault tree theory are used in these examples. Total risk assessment and resource allocation and safety performance trend analysis are discussed

  1. Risk management at university

    OpenAIRE

    Ivanova, H.; Abramovich, S.

    2013-01-01

    This article observes the basic recommendations for the risk management system in higher education as an example Yanka Kupala State University of Grodno. Consider the risk-management standard that based in a process approach

  2. Technical risk and society

    International Nuclear Information System (INIS)

    Lindackers, K.H.

    1983-01-01

    The report explains the possibilities and limits of risk analysis, risk assessment by the citizen, especially in hearings in the course of licensing procedures, and decisive causes why assessments on the part of the citizens may fail. (HP) [de

  3. Management of business risks

    OpenAIRE

    BAZARBAY A.

    2015-01-01

    The article presents methodological ideas concerning the problem of risk management. Special attention is paid to increasing of enterprises' operating efficiency by means of risk-management system development in business organizations.

  4. Fuzzy risk matrix

    International Nuclear Information System (INIS)

    Markowski, Adam S.; Mannan, M. Sam

    2008-01-01

    A risk matrix is a mechanism to characterize and rank process risks that are typically identified through one or more multifunctional reviews (e.g., process hazard analysis, audits, or incident investigation). This paper describes a procedure for developing a fuzzy risk matrix that may be used for emerging fuzzy logic applications in different safety analyses (e.g., LOPA). The fuzzification of frequency and severity of the consequences of the incident scenario are described which are basic inputs for fuzzy risk matrix. Subsequently using different design of risk matrix, fuzzy rules are established enabling the development of fuzzy risk matrices. Three types of fuzzy risk matrix have been developed (low-cost, standard, and high-cost), and using a distillation column case study, the effect of the design on final defuzzified risk index is demonstrated

  5. Canadian nuclear risk experience

    International Nuclear Information System (INIS)

    Hamel, P.E.

    1982-05-01

    Risk assessment in the Canadian nuclear fuel cycle is a very important and complex subject. Many levels of government are involved in deciding the acceptable limits for the risks, taking into account the benefits for society [fr

  6. [Global risk management].

    Science.gov (United States)

    Sghaier, W; Hergon, E; Desroches, A

    2015-08-01

    Risk management is a fundamental component of any successful company, whether it is in economic, societal or environmental aspect. Risk management is an especially important activity for companies that optimal security challenge of products and services is great. This is the case especially for the health sector institutions. Risk management is therefore a decision support tool and a means to ensure the sustainability of an organization. In this context, what methods and approaches implemented to manage the risks? Through this state of the art, we are interested in the concept of risk and risk management processes. Then we focus on the different methods of risk management and the criteria for choosing among these methods. Finally we highlight the need to supplement these methods by a systemic and global approach including through risk assessment by the audits. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. Stroke - risk factors

    Science.gov (United States)

    ... oxygen. Brain cells can die, causing lasting damage. Risk factors are things that increase your chance of ... a disease or condition. This article discusses the risk factors for stroke and things you can do ...

  8. Risk and cognition

    CERN Document Server

    Faucher, Colette

    2015-01-01

    This book presents recent research using cognitive science to apprehend risk situations and elaborate new organizations, new systems and new methodological tools in response. The book demonstrates the reasons, advantages and implications of the association of the concepts of cognition and risk. It is shown that this association has strong consequences on how to apprehend critical situations that emerge  within various activity domains, and how to elaborate responses to these critical situations.. The following topics are covered by the book: ·     Influence of the culture in risk management, ·     Influence of the risk communication in risk management, ·     User-centred design to improve risk situation management, ·     Designing new tools to assist risk situation management, ·     Risk prevention in industrial activities.

  9. Risk a multidisciplinary introduction

    CERN Document Server

    Straub, Daniel; Welpe, Isabell

    2014-01-01

    This is a unique book addressing the integration of risk methodology from various fields. It stimulates intellectual debate and communication across disciplines, promotes better risk management practices and contributes to the development of risk management methodologies. Book chapters explain fundamental risk models and measurement, and address risk and security issues from diverse areas such as finance and insurance, health sciences, life sciences, engineering and information science. Integrated Risk Sciences is an emerging field, that considers risks in different fields aiming at a common language, and at sharing and improving methods developed in different fields. Readers should have a Bachelor degree and at least one basic university course in statistics and probability. The main goal of the book is to provide basic knowledge on risk and security in a common language; the authors have taken particular care to ensure that each chapter can be understood by doctoral students and researchers across disciplin...

  10. Risk in International Business

    OpenAIRE

    Canavan, Deirdre; Sharkey Scott, Pamela

    2012-01-01

    Risk in international business can stress risk adverse behaviour to counteract foreign market uncertainty or individual entrepreneurial risk taking behaviour dependent on the characteristics of both the business sector and the individual. International business theory would suggest that the perception of risk may differ in situations including where new market entry is incremental, is taken in larger or earlier stages, or indeed whether it may be experienced in a continually fluctuating manne...

  11. Risk estimates for bone

    International Nuclear Information System (INIS)

    Schlenker, R.A.

    1982-01-01

    Bone sarcoma data for 226 228 Ra and 224 Ra are analyzed within the dosage ranges where the observed risk is zero. The uncertainty in the risk may be effectively illustrated by using pairs of functions based on a statistically-based measure of confidence. For radiation protection, the appropriate measure of risk is cumulative incidence in the presence of competing risks, as this takes into account the reduction of radiation effects brought about by natural mortality

  12. Measuring Systemic Risk

    DEFF Research Database (Denmark)

    Acharya, Viral V.; Heje Pedersen, Lasse; Philippon, Thomas

    2017-01-01

    We present an economic model of systemic risk in which undercapitalization of the financial sector as a whole is assumed to harm the real economy, leading to a systemic risk externality. Each financial institution’s contribution to systemic risk can be measured as its systemic expected shortfall...... of components of SES to predict emerging systemic risk during the financial crisis of 2007–2009....

  13. Credit risk transfer

    OpenAIRE

    Bank for International Settlements

    2003-01-01

    Executive summary Techniques for transferring credit risk, such as financial guarantees and credit insurance, have been a long-standing feature of financial markets. In the past few years, however, the range of credit risk transfer (CRT) instruments and the circumstances in which they are used have widened considerably. A number of factors have contributed to this growth, including: greater focus by banks and other financial institutions on risk management; a more rigorous approach to risk/re...

  14. Risk management for whales

    OpenAIRE

    Cont, R; Wagalath, L

    2016-01-01

    We propose framework for modeling portfolio risk which integrates market risk with liquidation costs which may arise in stress scenarios. Our model provides a systematic method for computing liquidation-adjusted risk measures for a portfolio. Calculation of Liquidation-adjusted VaR (LVaR) for sample portfolios reveals a substantial impact of liquidation costs on portfolio risk for portfolios with large concentrated positions.

  15. Risks and perceptions

    International Nuclear Information System (INIS)

    Lee, T.

    1987-01-01

    The article on the risks and perceptions of nuclear power was previously published in the Times Higher Education Supplement, May 1987. The public attitude towards risks associated with nuclear power, compared with other risks in everyday life, is examined. Results of psychological studies of the perceived risk of nuclear power are also discussed. The author argues that fear of nuclear catastrophe is not one which can be brushed aside by statistics or punditry. (UK)

  16. Communication about risks

    International Nuclear Information System (INIS)

    1988-01-01

    The conditions, difficulties and possibilities of communication on technological risks are detailed here. There is a description of the types and levels of argument on risks and the risk-concept itself, of the research field of risk communication, of the conceptional frame-work of the working-party, of the research programme and of the chances for a long-term prospect from the group. (DG) [de

  17. IT Risk register

    OpenAIRE

    Kohout, Karel

    2011-01-01

    The theoretical part of the thesis analyzes several selected methodologies and best-practices related to information technology risks management, with focus on documents and guidance developed by ISACA. It builds a set of ideas and basic requirements for effective model of an IT risk register. Strong emphasis is placed on mapping CobiT 4.1 based Risk IT to COBIT 5. The practical part describes implementation of an exploratory web-based IT risk register in Python programming language utilizing...

  18. Nuclear benefits and risks

    Energy Technology Data Exchange (ETDEWEB)

    Saunders, P

    1987-03-01

    The paper reviews the broader issues that affect nuclear power in a world energy context. The importance of nuclear power as an energy source is described, as well as the environmental effects of different energy sources. The risks associated with the nuclear industry are discussed with respect to: risks due to radiation exposure, risks to workers in the nuclear industry, and risks to the public due to discharges from nuclear installations. (U.K.).

  19. Perception of radiation risks

    International Nuclear Information System (INIS)

    Brenot, J.

    1992-01-01

    Perception of risks by people depends on many factors, either characterizing the individuals, or specific to the risk sources. The risk concept, which confuses the issue, is precised first. Second, the perception phenomenon is presented as an interactive process involving the individual, the hazard, and the social context. Third, dimensions of perception are listed and used to describe the perception of radiation risks. Finally, the relation between perception and attitude is clarified. (author) 50 refs

  20. Modern bank's credit risk

    Directory of Open Access Journals (Sweden)

    Šabović Šerif

    2015-01-01

    Full Text Available Credit risk is the most important risk banks have to face with. It occurs due to an obligation created because of debtors' capital and interest rate nonpayment. Debtors obligations non-fulfilment may lead to great losses and insolvency in bank's business. Credit risk is the crucial reason of bank's insolvency. Over 80% of bank's balance sheet is exposed to credit risk.

  1. Cardiovascular risk calculation

    African Journals Online (AJOL)

    James A. Ker

    2014-08-20

    Aug 20, 2014 ... smoking and elevated blood sugar levels (diabetes mellitus). These risk ... These are risk charts, e.g. FRS, a non-laboratory-based risk calculation, and ... for hard cardiovascular end-points, such as coronary death, myocardial ...

  2. Business history and risk

    OpenAIRE

    Terry Gourvish

    2003-01-01

    CARR, in association with the Centre for Business History, University of Leeds, held a successful workshop on 'Business History and Risk' on 20 February 2002. The workshop, which was sponsored by the ESRC, brought together business historians, economists, accountants and risk analysts to develop an interdisciplinary discussion on understandings of risk by employers, workers and governments in different historical settings.

  3. Cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Graversen, Peter; Abildstrøm, Steen Z.; Jespersen, Lasse

    2016-01-01

    Aim European society of cardiology (ESC) guidelines recommend that cardiovascular disease (CVD) risk stratification in asymptomatic individuals is based on the Systematic Coronary Risk Evaluation (SCORE) algorithm, which estimates individual 10-year risk of death from CVD. We assessed the potential...

  4. Readings in risk

    National Research Council Canada - National Science Library

    Glickman, Theodore S; Gough, Michael

    1990-01-01

    ... from Resources for the Future are distributed worldwide by The Johns Hopkins University Press. Library of Congress Cataloging-in-Publication Data Readings in risk I Theodore S. Glickman and Michael Gough, editors. p. cm. Includes bibliographical references. ISBN 0-915707-55-1 (alk. paper) 1. Technology-Risk assessment. 2. Health risk assessment....

  5. Contact Lens Risks

    Science.gov (United States)

    ... There is a risk of eye infection from bacteria in swimming pool water, hot tubs, lakes and the ocean Replace your contact lens storage case every 3 months or as directed by your eye care professional. Other Risks of Contact Lenses Other risks of contact lenses include pink eye ( ...

  6. Financial Risk Management

    OpenAIRE

    Catalin-Florinel Stanescu; Laurentiu Mircea Simion

    2011-01-01

    Concerns about the financial risk is increasing. In this climate, companies of all types and sizes want a robust framework for financial risk management to meet compliance requirements, contribute to better decision making and increase performance. Financial risk management professionals working with financial institutions and other corporate clients to achieve these objectives.

  7. Business risk management

    International Nuclear Information System (INIS)

    Cosby, C.

    2015-01-01

    Bruce Power's definition: an emerging and demonstrable event or change in business plan assumptions that could impact Bruce Power's achievement of its business plan objectives and results. Risks can be either negative (threats) or positive (opportunities). Risks against the 5 year business plan Net Risk = impact * probability.

  8. Business risk management

    Energy Technology Data Exchange (ETDEWEB)

    Cosby, C., E-mail: Christine.cosby@brucepower.com [Bruce Power, Tiverton, ON (Canada)

    2015-07-01

    Bruce Power's definition: an emerging and demonstrable event or change in business plan assumptions that could impact Bruce Power's achievement of its business plan objectives and results. Risks can be either negative (threats) or positive (opportunities). Risks against the 5 year business plan Net Risk = impact * probability.

  9. Risk assessment [Chapter 9

    Science.gov (United States)

    Dennis S. Ojima; Louis R. Iverson; Brent L. Sohngen; James M. Vose; Christopher W. Woodall; Grant M. Domke; David L. Peterson; Jeremy S. Littell; Stephen N. Matthews; Anantha M. Prasad; Matthew P. Peters; Gary W. Yohe; Megan M. Friggens

    2014-01-01

    What is "risk" in the context of climate change? How can a "risk-based framework" help assess the effects of climate change and develop adaptation priorities? Risk can be described by the likelihood of an impact occurring and the magnitude of the consequences of the impact (Yohe 2010) (Fig. 9.1). High-magnitude impacts are always...

  10. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...

  11. Risk Assessment and Integration Team (RAIT) Portfolio Risk Analysis Strategy

    Science.gov (United States)

    Edwards, Michelle

    2010-01-01

    Impact at management level: Qualitative assessment of risk criticality in conjunction with risk consequence, likelihood, and severity enable development of an "investment policy" towards managing a portfolio of risks. Impact at research level: Quantitative risk assessments enable researchers to develop risk mitigation strategies with meaningful risk reduction results. Quantitative assessment approach provides useful risk mitigation information.

  12. Synthetic risks, risk potency, and carcinogen regulation.

    Science.gov (United States)

    Viscusi, W K; Hakes, J K

    1998-01-01

    This article analyzes a comprehensive sample of over 350 chemicals tested for carcinogenicity to assess the determinants of the probability of regulation. Controlling for differences in the risk potency and noncancer risks, synthetic chemicals have a significantly higher probability of regulation overall: this is due to the greater likelihood of U.S. Food and Drug Administration (FDA) regulation. Measures of risk potency increase the probability of regulation by the U.S. Environmental Protection Agency (EPA), have a somewhat weaker positive effect on regulation by the U.S. Occupational Safety and Health Administration (OSHA), and decrease the likelihood of regulation by the FDA. The overall regulatory pattern is one in which the FDA targets synthetic chemicals and chemicals that pose relatively minor cancer risk. The EPA particularly performed more sensibly than many critics have suggested.

  13. Risk indices in comparative risk assessment studies

    International Nuclear Information System (INIS)

    Hubert, P.

    1984-01-01

    More than a decade ago the development of comparative risk assessment studies aroused overwhelming interest. There was no doubt that data on the health and safety aspects of energy systems would greatly benefit, or even end, the debate on nuclear energy. Although such attempts are still strongly supported, the rose-coloured expectations of the early days have faded. The high uncertainties, and the contradictory aspect, of the first results might explain this evolution. The loose connection between the range of computed risk indices and the questions on which the debate was focused is another reason for this decline in interest. Important research work is being carried out aiming at reducing the different kinds of uncertainties. Rather than the uncertainties, the paper considers the meaning of available risk indices and proposes more significant indices with respect to the goals of risk assessment. First, the indices which are of frequent use in comparative studies are listed. The stress is put on a French comparative study from which most examples are drawn. Secondly, the increase in magnitude of the indices and the decrease in the attributability of the risk to a given system is shown to be a consequence of the trend towards more comprehensive analyses. Thirdly, the ambiguity of such indices as the collective occupational risk is underlined, and a possible solution is suggested. Whenever risk assessments are related to pragmatic decision making problems it is possible to find satisfactory risk indices. The development of cost-effectiveness analyses and the proposals for quantitative safety goals clearly demonstrate this point. In the field of comparison of social impacts some proposals are made, but there remain some gaps still to be filled. (author)

  14. Risk Assessment Overview

    Science.gov (United States)

    Prassinos, Peter G.; Lyver, John W., IV; Bui, Chinh T.

    2011-01-01

    Risk assessment is used in many industries to identify and manage risks. Initially developed for use on aeronautical and nuclear systems, risk assessment has been applied to transportation, chemical, computer, financial, and security systems among others. It is used to gain an understanding of the weaknesses or vulnerabilities in a system so modification can be made to increase operability, efficiency, and safety and to reduce failure and down-time. Risk assessment results are primary inputs to risk-informed decision making; where risk information including uncertainty is used along with other pertinent information to assist management in the decision-making process. Therefore, to be useful, a risk assessment must be directed at specific objectives. As the world embraces the globalization of trade and manufacturing, understanding the associated risk become important to decision making. Applying risk assessment techniques to a global system of development, manufacturing, and transportation can provide insight into how the system can fail, the likelihood of system failure and the consequences of system failure. The risk assessment can identify those elements that contribute most to risk and identify measures to prevent and mitigate failures, disruptions, and damaging outcomes. In addition, risk associated with public and environment impact can be identified. The risk insights gained can be applied to making decisions concerning suitable development and manufacturing locations, supply chains, and transportation strategies. While risk assessment has been mostly applied to mechanical and electrical systems, the concepts and techniques can be applied across other systems and activities. This paper provides a basic overview of the development of a risk assessment.

  15. Screening Risk Evaluation methodology

    International Nuclear Information System (INIS)

    Hopper, K.M.

    1994-01-01

    The Screening Risk Evaluation (SRE) Guidance document is a set of guidelines provided for the uniform implementation of SREs performed on D ampersand D facilities. These guidelines are designed specifically for the completion of the second (semi-quantitative screening) phase of the D ampersand D Risk-Based Process. The SRE Guidance produces screening risk scores reflecting levels of risk through the use of risk ranking indices. Five types of possible risk are calculated from the SRE: current releases, worker exposures, future releases, physical hazards, and criticality. The Current Release Index (CRI) calculates the risk to human health and the environment from ongoing or probable releases within a one year time period. The Worker Exposure Index (WEI) calculates the risk to workers, occupants, and visitors in D ampersand D facilities of contaminant exposure. The Future Release Index (FRI) calculates the risk of future releases of contaminants, after one year, to human health and the environment. The Physical Hazards Index (PHI) calculates the risk-to human health due to factors other than that of contaminants. The index of Criticality is approached as a modifying factor to the entire SRE, due to the fact that criticality issues are strictly regulated under DOE. Screening risk results will be tabulated in matrix form and Total Risk will be calculated (weighted equation) to produce a score on which to base early action recommendations. Other recommendations from the screening risk scores will be made based either on individual index scores or from reweighted Total Risk calculations. All recommendations based on the SRE will be made based on a combination of screening risk scores, decision drivers, and other considerations, determined on a project by project basis. The SRE is the first and most important step in the overall D ampersand D project level decision making process

  16. The human papillomavirus type 11 and 16 E6 proteins modulate the cell-cycle regulator and transcription cofactor TRIP-Br1

    International Nuclear Information System (INIS)

    Gupta, Sanjay; Takhar, Param Parkash S; Degenkolbe, Roland; Heng Koh, Choon; Zimmermann, Holger; Maolin Yang, Christopher; Guan Sim, Khe; I-Hong Hsu, Stephen; Bernard, Hans-Ulrich

    2003-01-01

    The genital human papillomaviruses (HPVs) are a taxonomic group including HPV types that preferentially cause genital and laryngeal warts ('low-risk types'), such as HPV-6 and HPV-11, or cancer of the cervix and its precursor lesions ('high-risk types'), such as HPV-16. The transforming processes induced by these viruses depend on the proteins E5, E6, and E7. Among these oncoproteins, the E6 protein stands out because it supports a particularly large number of functions and interactions with cellular proteins, some of which are specific for the carcinogenic HPVs, while others are shared among low- and high-risk HPVs. Here we report yeast two-hybrid screens with HPV-6 and -11 E6 proteins that identified TRIP-Br1 as a novel cellular target. TRIP-Br1 was recently detected by two research groups, which described two separate functions, namely that of a transcriptional integrator of the E2F1/DP1/RB cell-cycle regulatory pathway (and then named TRIP-Br1), and that of an antagonist of the cyclin-dependent kinase suppression of p16INK4a (and then named p34SEI-1). We observed that TRIP-Br1 interacts with low- and high-risk HPV E6 proteins in yeast, in vitro and in mammalian cell cultures. Transcription activation of a complex consisting of E2F1, DP1, and TRIP-Br1 was efficiently stimulated by both E6 proteins. TRIP-Br1 has an LLG E6 interaction motif, which contributed to the binding of E6 proteins. Apparently, E6 does not promote degradation of TRIP-Br1. Our observations imply that the cell-cycle promoting transcription factor E2F1/DP1 is dually targeted by HPV oncoproteins, namely (i) by interference of the E7 protein with repression by RB, and (ii) by the transcriptional cofactor function of the E6 protein. Our data reveal the natural context of the transcription activator function of E6, which has been predicted without knowledge of the E2F1/DP1/TRIP-Br/E6 complex by studying chimeric constructs, and add a function to the limited number of transforming properties shared

  17. Individual Property Risk Management

    Directory of Open Access Journals (Sweden)

    Michael S. Finke

    2010-01-01

    Full Text Available This paper reviews household property risk management and estimates normatively optimal choice under theoretical assumptions. Although risk retention limits are common in the financial planning industry, estimates of optimal risk retention that include both financial and human wealth far exceed limits commonly recommended. Households appear to frame property losses differently from other wealth losses leading to wealth-reducing, excess risk transfer. Possible theoretical explanations for excess sensitivity to loss are reviewed. Differences between observed and optimal risk management imply a large potential gain from improved choice.

  18. Life without risk?

    International Nuclear Information System (INIS)

    Hohlneicher, G.; Raschke, E.

    1989-01-01

    Mankind's sensitivity to new, global threats, to chemical and radioactive pollution and to interventions in the biological process actually gives rise to a one-sided and narrow range of reactions. Demands for zero-risk make one forget that a reduced risk many possibly lead to a far more dangerous risk in another place. That no uniform view of things can arise in this way is shown by these articles, from the areas of science, politics and the arts, on questions of world population, waste management, climatic change, genetic manipulation, philosophical and ethical problems of risk acceptance as well as the responsibility for risks. (DG) [de

  19. Agile risk management

    CERN Document Server

    Moran, Alan

    2014-01-01

    This work is the definitive guide for IT managers and agile practitioners. It elucidates the principles of agile risk management and how these relate to individual projects. Explained in clear and concise terms, this synthesis of project risk management and agile techniques is illustrated using the major methodologies such as XP, Scrum and DSDM.Although the agile community frequently cites risk management, research suggests that risk is often narrowly defined and, at best, implicitly treated, which in turn leads to an inability to make informed decisions concerning risk and reward and a poor u

  20. FOREIGN CURRENCY RISK HEDGING

    Directory of Open Access Journals (Sweden)

    Mihaela SUDACEVSCHI

    2017-05-01

    Full Text Available This paper presents the traditional types of exchange rate risk faced by firms and some of principal methods of exchange risk management that a company which make foreign currency operations can use. Foreign currency risk management involves both assessing the risk faced by the companies and adopting measures for the risk hedging or reduce the damage it may cause. The damages result from the company’s unfavorable difference between the exchange rates of the currencies in which the transactions are made.

  1. riskRegression

    DEFF Research Database (Denmark)

    Ozenne, Brice; Sørensen, Anne Lyngholm; Scheike, Thomas

    2017-01-01

    In the presence of competing risks a prediction of the time-dynamic absolute risk of an event can be based on cause-specific Cox regression models for the event and the competing risks (Benichou and Gail, 1990). We present computationally fast and memory optimized C++ functions with an R interface...... for predicting the covariate specific absolute risks, their confidence intervals, and their confidence bands based on right censored time to event data. We provide explicit formulas for our implementation of the estimator of the (stratified) baseline hazard function in the presence of tied event times. As a by...... functionals. The software presented here is implemented in the riskRegression package....

  2. Risk management in Takaful

    OpenAIRE

    Akhter, Waheed

    2010-01-01

    Risk management is of vital importance in Islam and Takāful provides a way to manage risks in business according to Sharī’ah principles. This research paper attempts to identify various types of risks involved in Takāful business that affect operational and investment functions of Takāful operators across the globe. It lays down criteria for Takāful operator to manage those risks effectively. However, Takāful operators often face difficulty in managing market and credit risks as Sharī’ah comp...

  3. MASTERING SUPPLY CHAIN RISKS

    Directory of Open Access Journals (Sweden)

    Borut Jereb

    2012-11-01

    Full Text Available Risks in supply chains represent one of the major business issues today. Since every organizationstrives for success and uninterrupted operations, efficient supply chain risk management is crucial.During supply chain risk research at the Faculty of Logistics in Maribor (Slovenia some keyissues in the field were identified, the major being the lack of instruments which can make riskmanagement in an organization easier and more efficient. Consequently, a model which captures anddescribes risks in an organization and its supply chain was developed. It is in accordance with thegeneral risk management and supply chain security standards, the ISO 31000 and ISO 28000families. It also incorporates recent finding from the risk management field, especially from theviewpoint of segmenting of the public.The model described in this paper focuses on the risks itself by defining them by different keydimensions, so that risk management is simplified and can be undertaken in every supply chain andorganizations within them. Based on our mode and consequent practical research in actualorganizations, a freely accessible risk catalog has been assembled and published online from the risksthat have been identified so far. This catalog can serve as a checklist and a starting point in supplychain risk management in organizations. It also incorporates experts from the field into a community,in order to assemble an ever growing list of possible risks and to provide insight into the model andits value in practice.

  4. Biosafety Risk Assessment Methodology

    Energy Technology Data Exchange (ETDEWEB)

    Caskey, Susan Adele [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). International Biological Threat Reduction Program; Gaudioso, Jennifer M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). International Biological Threat Reduction Program; Salerno, Reynolds Mathewson [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). International Biological Threat Reduction Program; Wagner, Stefan M. [Public Health Agency of Canada, Winnipeg, MB (Canada). Canadian Science Centre for Human and Animal Health (CSCHAH); Shigematsu, Mika [National Inst. of Infectious Diseases (NIID), Tokyo (Japan); Risi, George [Infectious Disease Specialists, P.C, Missoula, MT (United States); Kozlovac, Joe [US Dept. of Agriculture (USDA)., Beltsville, MD (United States); Halkjaer-Knudsen, Vibeke [Statens Serum Inst., Copenhagen (Denmark); Prat, Esmeralda [Bayer CropScience, Monheim am Rhein (Germany)

    2010-10-01

    Laboratories that work with biological agents need to manage their safety risks to persons working the laboratories and the human and animal community in the surrounding areas. Biosafety guidance defines a wide variety of biosafety risk mitigation measures, which include measures which fall under the following categories: engineering controls, procedural and administrative controls, and the use of personal protective equipment; the determination of which mitigation measures should be used to address the specific laboratory risks are dependent upon a risk assessment. Ideally, a risk assessment should be conducted in a manner which is standardized and systematic which allows it to be repeatable and comparable. A risk assessment should clearly define the risk being assessed and avoid over complication.

  5. Perception of nuclear risks

    International Nuclear Information System (INIS)

    Brenot, J.; Bonnefous, S.; Hubert, Ph.

    1996-01-01

    Many factors are involved in the perception of a risk by individuals. Some are individual related (psychology, knowledge, experience), others describe the social environment (culture, ideology), others at end precise the nature of the risk. The word risk has various meanings and is understood differently by the three main categories involved in risk management, that is engineers, administrators and lay public. Several models which describe the perception phenomenon are presented. The dimensions affecting perception are listed. Based on public opinion poll data, a risk taxonomy is proposed, perceived nuclear risks are compared with other risks, and results are given concerning trust in the information diffused and the credibility of those in charge of nuclear activities. (author)

  6. Measuring Idiosyncratic Risk

    DEFF Research Database (Denmark)

    Sunesen, Eva Rytter

    This paper offers two refinements of the traditional risk measure based on the volatility of growth. First, we condition GDP growth on structural characteristics of the host country that move only slowly and therefore can be partly predicted by an investor. Second, we adjust conditional risk...... for the systematic components due to the global and regional interdependence between alternative investment locations. The decomposition of conditional risk into its systematic and idiosyncratic components reveals that not only are African countries on average characterised by a larger conditional risk than Asian...... and Latin American countries, but the idiosyncratic risk factor also represents a larger share than in other developing countries. As a final contribution, we search the empirical literature on foreign direct investment and risk in order to determine which of the suggested risk measures provide the best...

  7. Low Risk Anomalies?

    DEFF Research Database (Denmark)

    Schneider, Paul; Wagner, Christian; Zechner, Josef

    This paper shows theoretically and empirically that beta- and volatility-based low risk anomalies are driven by return skewness. The empirical patterns concisely match the predictions of our model that endogenizes the role of skewness for stock returns through default risk. With increasing downside...... risk, the standard capital asset pricing model (CAPM) increasingly overestimates expected equity returns relative to firms' true (skew-adjusted) market risk. Empirically, the profitability of betting against beta/volatility increases with firms' downside risk, and the risk-adjusted return differential...... of betting against beta/volatility among low skew firms compared to high skew firms is economically large. Our results suggest that the returns to betting against beta or volatility do not necessarily pose asset pricing puzzles but rather that such strategies collect premia that compensate for skew risk...

  8. Social amplification of risk

    International Nuclear Information System (INIS)

    Kasperson, R.E.; Renn, O.; Slovic, P.; Kasperson, J.X.; Emani, S.

    1989-01-01

    The risks associated with radioactive and other hazardous waste disposal may be expected to interact with societal processes to enlarge or attenuate the consequences of risks and risk events. This article summarizes a conceptual framework that depicts the social amplification of risk. Using a data base of 128 hazard events that have occurred largely over the past ten years, the authors examine the role of physical consequences, media coverage, and public perceptions of risk in generating social and economic impacts. The analysis concludes that social amplification processes substantially shape the nature and magnitude of those impacts but also that such social amplification appears to be systematically related to characteristics of the risks and risk events

  9. Limit lines for risk

    International Nuclear Information System (INIS)

    Cox, D.C.; Baybutt, P.

    1982-01-01

    Approaches to the regulation of risk from technological systems, such as nuclear power plants or chemical process plants, in which potential accidents may result in a broad range of adverse consequences must take into account several different aspects of risk. These include overall or average risk, accidents posing high relative risks, the rate at which accident probability decreases with increasing accident consequences, and the impact of high frequency, low consequence accidents. A hypothetical complementary cumulative distribution function (CCDF), with appropriately chosen parametric form, meets all these requirements. The Farmer limit line, by contrast, places limits on the risks due to individual accident sequences, and cannot adequately account for overall risk. This reduces its usefulness as a regulatory tool. In practice, the CCDF is used in the Canadian nuclear licensing process, while the Farmer limit line approach, supplemented by separate qualitative limits on overall risk, is employed in the United Kingdom

  10. Offshore risk assessment

    CERN Document Server

    Vinnem, Jan-Erik

    2014-01-01

      Offshore Risk Assessment was the first book to deal with quantified risk assessment (QRA) as applied specifically to offshore installations and operations. Risk assessment techniques have been used for more than three decades in the offshore oil and gas industry, and their use is set to expand increasingly as the industry moves into new areas and faces new challenges in older regions.   This updated and expanded third edition has been informed by a major R&D program on offshore risk assessment in Norway and summarizes research from 2006 to the present day. Rooted with a thorough discussion of risk metrics and risk analysis methodology,  subsequent chapters are devoted to analytical approaches to escalation, escape, evacuation and rescue analysis of safety and emergency systems.   Separate chapters analyze the main hazards of offshore structures: fire, explosion, collision, and falling objects as well as structural and marine hazards. Risk mitigation and control are discussed, as well as an illustrat...

  11. Overview of risk assessment

    International Nuclear Information System (INIS)

    Rimington, J.D.

    1992-01-01

    The paper begins by defining some terms, and then refer to a number of technical and other difficulties. Finally it attempts to set out why risk assessment is important and what its purposes are. 2) First, risk and risk assessment - what are they?. 3) Risk is a subject of universal significance. Life is very uncertain, and we can achieve no object or benefit in it except by approaching nearer to particular hazards which lie between us and our objects. That approach represents acceptance of risk. 4) Risk assessment is a way of systematising our approach to hazard with a view to determining what is more and what is less risky. It helps us in the end to diminish our exposure while obtaining whatever benefits we have in mind, or to optimise the risks and the benefits

  12. Overview of risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Rimington, J D [Health and Safety Executive (United Kingdom)

    1992-07-01

    The paper begins by defining some terms, and then refer to a number of technical and other difficulties. Finally it attempts to set out why risk assessment is important and what its purposes are. 2) First, risk and risk assessment - what are they?. 3) Risk is a subject of universal significance. Life is very uncertain, and we can achieve no object or benefit in it except by approaching nearer to particular hazards which lie between us and our objects. That approach represents acceptance of risk. 4) Risk assessment is a way of systematising our approach to hazard with a view to determining what is more and what is less risky. It helps us in the end to diminish our exposure while obtaining whatever benefits we have in mind, or to optimise the risks and the benefits.

  13. Models of Credit Risk Measurement

    OpenAIRE

    Hagiu Alina

    2011-01-01

    Credit risk is defined as that risk of financial loss caused by failure by the counterparty. According to statistics, for financial institutions, credit risk is much important than market risk, reduced diversification of the credit risk is the main cause of bank failures. Just recently, the banking industry began to measure credit risk in the context of a portfolio along with the development of risk management started with models value at risk (VAR). Once measured, credit risk can be diversif...

  14. An Estimation of Risk Impact of Anticipated Transients without Scram for a KSNP

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seok Jung; Yang Joon Eon

    2006-07-15

    Anticipated transient without scram (ATWS) event is an accident sequence with large risk impact, while it is a beyond design basis accident (BDBA). We have estimated a risk due to an ATWS accident sequence for the KSNP in consideration of the recent accident analysis results. The SECY-83-293's model for the CE type plants has been used in a risk estimation of ATWS. A risk estimation due to an ATWS for the KSNP has been performed in consideration of the recent ATWS accident analysis results and plant information. We reviewed influence factors in the SECY-83-293's model, these factors have been re-estimated by using current information and PSA results for a KSNP. A risk due to an ATWS has been estimated as 3.6E-6/yr of CDF by using domestic aspect and recent KSNP information. A sensitivity study for the UET variation has been performed. As the results of the sensitivity analysis, the overall risk spectrum by the UET variation is bounded between 7.80E-7/yr to 8.00E-6/yr of CDF. As the result of the current study, the risk due to an ATWS accident sequence has been identified as a considerable impact on the entire risk of a KSNP, so the risk estimation of that plant should be upgraded by considering the recent information like the ATWS accident analysis results. Finally, we expect that this study can become a basis for the entire risk estimation of the referred plant.

  15. Risk perception and risk communication: lessons learned

    International Nuclear Information System (INIS)

    Baillif, L.; Sackur, J.

    1998-01-01

    Industry can master risks but it cannot master the representations people have of these risks. This is why distortions may occur, as the public perceives risks where they are not, or in a totally deformed way. To deal with this type of situation which is dangerous in the long run, both for society and industry, it is necessary to study in detail where and how the difference between real risks and perceived risks is introduced. It then becomes possible to determine what means of action are available to manage the representations and the perceptions of risks. We shall mention two rather different examples of type of direct contact with the industrial reality; in France, we have determined policy of visits of nuclear sites (more than 10 000 people visit Cogema- la Hague site yearly), mainly addressed to school children and people living in the vicinity of the site. During these visits there is of course no question of explaining the detailed operation of the facility or the risks it generates. The purpose is to make the representation of the nuclear industry just as familiar as the representation of another large-scale technology tool: trains, dams,. In a different manner, missions are organised by Cogema - B.N.F.L.- O.R.C. (Overseas reprocessing Committee) to de dramatize the transport of high level vitrified wastes from Europe to Japan. these missions travel through those countries the ship come close to. Here, again, although the target is more the relays of opinion, the effective presence of specialized transport ship is a crucial element in putting a halt to phantasmic representations, as they are born from the remoteness of the object. (N.C.)

  16. Component of the risk analysis

    International Nuclear Information System (INIS)

    Martinez, I.; Campon, G.

    2013-01-01

    The power point presentation reviews issues like analysis of risk (Codex), management risk, preliminary activities manager, relationship between government and industries, microbiological danger and communication of risk

  17. Risk Factors in Derivatives Markets

    Directory of Open Access Journals (Sweden)

    Raimonda Martinkutė-Kaulienė

    2015-02-01

    Full Text Available The objective of the article is to analyse and present the classification of risks actual to derivative securities. The analysis is based on classical and modern literature findings and analysis of newest statistical data. The analysis led to the conclusion, that the main risks typical for derivatives contracts and their traders are market risk, liquidity risk, credit and counterparty risk, legal risk and transactions risk. Pricing risk and systemic risk is also quite important. The analysis showed that market risk is the most important kind of risk that in many situations influences the level of remaining risks.

  18. Taking the Risk Out of Risk Assessment

    Science.gov (United States)

    2005-01-01

    The ability to understand risks and have the right strategies in place when risky events occur is essential in the workplace. More and more organizations are being confronted with concerns over how to measure their risks or what kind of risks they can take when certain events transpire that could have a negative impact. NASA is one organization that faces these challenges on a daily basis, as effective risk management is critical to the success of its missions especially the Space Shuttle missions. On July 29, 1996, former NASA Administrator Daniel Goldin charged NASA s Office of Safety and Mission Assurance with developing a probabilistic risk assessment (PRA) tool to support decisions on the funding of Space Shuttle upgrades. When issuing the directive, Goldin said, "Since I came to NASA [in 1992], we've spent billions of dollars on Shuttle upgrades without knowing how much they improve safety. I want a tool to help base upgrade decisions on risk." Work on the PRA tool began immediately. The resulting prototype, the Quantitative Risk Assessment System (QRAS) Version 1.0, was jointly developed by NASA s Marshall Space Flight Center, its Office of Safety and Mission Assurance, and researchers at the University of Maryland. QRAS software automatically expands the reliability logic models of systems to evaluate the probability of highly detrimental outcomes occurring in complex systems that are subject to potential accident scenarios. Even in its earliest forms, QRAS was used to begin PRA modeling of the Space Shuttle. In parallel, the development of QRAS continued, with the goal of making it a world-class tool, one that was especially suited to NASA s unique needs. From the beginning, an important conceptual goal in the development of QRAS was for it to help bridge the gap between the professional risk analyst and the design engineer. In the past, only the professional risk analyst could perform, modify, use, and perhaps even adequately understand PRA. NASA wanted

  19. Human papillomavirus 33 worldwide genetic variation and associated risk of cervical cancer

    Science.gov (United States)

    Chen, Alyce A.; Heideman, Daniëlle A.M.; Boon, Debby; Chen, Zigui; Burk, Robert D.; De Vuyst, Hugo; Gheit, Tarik; Snijders, Peter J.F.; Tommasino, Massimo; Franceschi, Silvia; Clifford, Gary M.

    2014-01-01

    Human papillomavirus (HPV) 33, a member of the HPV16-related alpha-9 species group, is found in approximately 5% of cervical cancers worldwide. The current study aimed to characterize the genetic diversity of HPV33 and to explore the association of HPV33 variants with the risk for cervical cancer. Taking advantage of the International Agency for Research on Cancer biobank, we sequenced the entire E6 and E7 open reading frames of 213 HPV33-positive cervical samples from 30 countries. We identified 28 HPV33 variants that formed 5 phylogenetic groups: the previously identified A1, A2, and B (sub) lineages and the novel A3 and C (sub)lineages. The A1 sublineage was strongly over-represented in cervical cases compared to controls in both Africa and Europe. In conclusion, we provide a classification system for HPV33 variants based on the sequence of E6 and E7 and suggest that the association of HPV33 with cervical cancer may differ by variant (sub)lineage. PMID:24314666

  20. High risk human papillomavirus in the periodontium : A case control study.

    Science.gov (United States)

    Shipilova, Anna; Dayakar, Manjunath Mundoor; Gupta, Dinesh

    2017-01-01

    Human papilloma viruses (HPVs) are small DNA viruses that have been identified in periodontal pocket as well as gingival sulcus. High risk HPVs are also associated with a subset of head and neck carcinomas. It is thought that the periodontium could be a reservoir for HPV. 1. Detection of Human Papilloma virus (HPV) in periodontal pocket as well as gingival of patients having localized chronic periodontitis and gingival sulcus of periodontally healthy subjects. 2. Quantitative estimation of E6 and E7 mRNA in subjects showing presence of HPV3. To assess whether periodontal pocket is a reservoir for HPV. This case-control study included 30 subjects with localized chronic Periodontitis (cases) and 30 periodontally healthy subjects (controls). Two samples were taken from cases, one from periodontal pocket and one from gingival sulcus and one sample was taken from controls. Samples were collected in the form of pocket scrapings and gingival sulcus scrapings from cases and controls respectively. These samples were sent in storage media for identification and estimation of E6/E7 mRNA of HPV using in situ hybridization and flow cytometry. Statistical analysis was done by using, mean, percentage and Chi Square test. A statistical package SPSS version 13.0 was used to analyze the data. P value oral cancer, periodontitis and HPV. However prospective studies are required to further explore this link.

  1. Competing risk theory and radiation risk assessment

    International Nuclear Information System (INIS)

    Groer, P.G.

    1980-01-01

    New statistical procedures are applied to estimate cumulative distribution functions (c.d.f.), force of mortality, and latent period for radiation-induced malignancies. It is demonstrated that correction for competing risks influences the shape of dose response curves, estimates of the latent period, and of the risk from ionizing radiations. The equivalence of the following concepts is demonstrated: force of mortality, hazard rate, and age or time specific incidence. This equivalence makes it possible to use procedures from reliability analysis and demography for radiation risk assessment. Two methods used by reliability analysts - hazard plotting and total time on test plots - are discussed in some detail and applied to characterize the hazard rate in radiation carcinogenesis. C.d.f.'s with increasing, decreasing, or constant hazard rate have different shapes and are shown to yield different dose-response curves for continuous irradiation. Absolute risk is shown to be a sound estimator only if the force of mortality is constant for the exposed and the control group. Dose-response relationships that use the absolute risk as a measure for the effect turn out to be special cases of dose-response relationships that measure the effect with cumulative incidence. (H.K.)

  2. GAR Global Risk Assessment

    Science.gov (United States)

    Maskrey, Andrew; Safaie, Sahar

    2015-04-01

    Disaster risk management strategies, policies and actions need to be based on evidence of current disaster loss and risk patterns, past trends and future projections, and underlying risk factors. Faced with competing demands for resources, at any level it is only possible to priorities a range of disaster risk management strategies and investments with adequate understanding of realised losses, current and future risk levels and impacts on economic growth and social wellbeing as well as cost and impact of the strategy. The mapping and understanding of the global risk landscape has been greatly enhanced by the latest iteration of the GAR Global Risk Assessment and the objective of this submission is to present the GAR global risk assessment which contributed to Global Assessment Report (GAR) 2015. This initiative which has been led by UNISDR, was conducted by a consortium of technical institutions from around the world and has covered earthquake, cyclone, riverine flood, and tsunami probabilistic risk for all countries of the world. In addition, the risks associated with volcanic ash in the Asia-Pacific region, drought in various countries in sub-Saharan Africa and climate change in a number of countries have been calculated. The presentation will share thee results as well as the experience including the challenges faced in technical elements as well as the process and recommendations for the future of such endeavour.

  3. Optimizing risk management

    International Nuclear Information System (INIS)

    Kindred, G.W.

    2000-01-01

    Commercial nuclear power plant management is focussed on the safe, efficient, economical production of electricity. To accomplish the safe aspect of the equation, risk must be determined for the operation and maintenance of the facility. To accomplish the efficient aspect of the equation, management must understand those risks and factor risk insights into their decision process. The final piece of the equation is economical which is accomplished by minimizing, plant outage durations and proper utilization of resources. Probabilistic Risk Assessment can provide the risk insights to accomplish all three; safety, efficiency, and economically. How? Safe production of electricity can be quantified by use of PRA modeling and other risk insights that can determine the core damage frequency. Efficient production of electricity can be influenced by providing management with quantified risk insights for use in decision making. And, one example of economical production of electricity is by not having over conservative deterministic based defense in depth approaches to system maintenance and availability. By using risk-informed insights nuclear safety can be quantified and risk can be managed. Confidence in this approach can be achieved by ensuring the content and quality of the PRA is standardized throughout the industry. The time has arrived for Probabilistic Risk Assessment to take an active position as a major role player in the safe, efficient, and economical operation of commercial nuclear power plants. (author)

  4. Risk of energy production

    International Nuclear Information System (INIS)

    Inhaber, Herbert.

    1978-03-01

    Every human activity involves risk of accident or disease. Generation of energy is no exception. Although such risk has been considered for conventional systems (coal, oil and nuclear), a similar analysis for the so-called alternative or non-conventional systems (solar, wind, ocean thermal and methanol) has been lacking. This paper presents an evaluation of the risk, both occupational and to the public, of non-conventional energy systems. They are considered both in absolute terms and in relation to conventional systems. The risk of most non-conventional systems, per unit of energy output, is comparable to, and in some cases much higher than, the risk from coal and oil. This conclusion holds whether we consider deaths or injuries. Nuclear power and natural gas had the lowest overall risk of the ten technologies considered. Ocean thermal energy ranked third. The surprising result is that the other seven technologies considered were found to be up to 100 times less safe. The total risk is calculated by considering six components: material acquisition and construction, emissions caused by material production, operation and maintenance, energy back-up, energy storage, and transportation. In this way the risk of widely different systems can be fairly assessed. This methodology of 'risk accounting' will not tell us which energy technology to use. However, it can be employed to inform society of the risk inherent in competing energy systems. (author)

  5. Operational risk assessment.

    Science.gov (United States)

    McKim, Vicky L

    2017-06-01

    In the world of risk management, which encompasses the business continuity disciplines, many types of risk require evaluation. Financial risk is most often the primary focus, followed by product and market risks. Another critical area, which typically lacks a thorough review or may be overlooked, is operational risk. This category encompasses many risk exposure types including those around building structures and systems, environmental issues, nature, neighbours, clients, regulatory compliance, network, data security and so on. At times, insurance carriers will assess internal hazards, but seldom do these assessments include more than a cursory look at other types of operational risk. In heavily regulated environments, risk assessments are required but may not always include thorough assessments of operational exposures. Vulnerabilities may linger or go unnoticed, only to become the catalyst for a business disruption at a later time, some of which are so severe that business recovery becomes nearly impossible. Businesses may suffer loss of clients as the result of a prolonged disruption of services. Comprehensive operational risk assessments can assist in identifying such vulnerabilities, exposures and threats so that the risk can be minimised or removed. This paper lays out how an assessment of this type can be successfully conducted.

  6. Risk-informed regulation

    International Nuclear Information System (INIS)

    Hoffman, D.R.

    2003-01-01

    In assessing safety for nuclear facilities, regulators have traditionally used a deterministic approach. New techniques for assessing nuclear or radiological risks make it possible for regulators to incorporate risk insights into their regulations. By 'risk-informing' the regulatory processes, independent bodies tasked with protecting the health and safety of the public can focus on those design and operational issues most important to safety. Such an approach is a move away from prescriptive regulations that were based on conservative engineering judgments toward regulations focused on issues that contribute significantly to safety. Despite the availability of probabilistic risk assessment (PRA) tools, organisations often struggle with how to best use this capability. Most international regulations are still based largely on deterministic analyses that were developed without the benefit of quantitative or measurable estimates of risk. PRA considers issues of risk in a more comprehensive manner by examining a wider spectrum of initiating events and their frequency, and considers the likelihood of events in a rigorous and comprehensive manner. In some countries, nuclear regulators are actively moving toward increasing the use of risk insights in a variety of strategic arenas, including risk-informed technical specifications (operating limits and conditions), in-service inspection and testing, programs, and assessment and enforcement actions. A risk-informed approach enhances the traditional deterministic approach by explicitly considering a broader range of safety challenges, focusing resources on the basis of risk significance, considering a broader range of counter measures to mitigate challenges, and explicitly identifying and quantifying uncertainties in analyses. (author)

  7. Managing risk at Hanford

    International Nuclear Information System (INIS)

    Hesser, W.A.; Stillwell, W.G.; Rutherford, W.A.

    1994-01-01

    Clearly, there is sufficient motivation from Washington for the Hanford community to pay particular attention to the risks associated with the substantial volumes of radiological, hazardous, and mixed waste at Hanford. But there is also another reason for emphasizing risk: Hanford leaders have come to realize that their decisions must consider risk and risk reduction if those decisions are to be technically sound, financially affordable, and publicly acceptable. The 560-square miles of desert land is worth only a few thousand dollars an acre (if that) -- hardly enough to justify the almost two billion dollars that will be spent at Hanford this year. The benefit of cleaning up the Hanford Site is not the land but the reduction of potential risk to the public and the environment for future generations. If risk reduction is our ultimate goal, decisions about priority of effort and resource allocation must consider those risks, now and in the future. The purpose of this paper is to describe how Hanford is addressing the issues of risk assessment, risk management, and risk-based decision making and to share some of our experiences in these areas

  8. Fuel related risks; Braenslerisker

    Energy Technology Data Exchange (ETDEWEB)

    Englund, Jessica; Sernhed, Kerstin; Nystroem, Olle; Graveus, Frank (Grontmij AB, (Sweden))

    2012-02-15

    The project, within which this work report was prepared, aimed to complement the Vaermeforsk publication 'Handbook of fuels' on fuel related risks and measures to reduce the risks. The fuels examined in this project where the fuels included in the first version of the handbook from 2005 plus four additional fuels that will be included in the second and next edition of the handbook. Following fuels were included: woodfuels (sawdust, wood chips, powder, briquettes), slash, recycled wood, salix, bark, hardwood, stumps, straw, reed canary grass, hemp, cereal, cereal waste, olive waste, cocoa beans, citrus waste, shea, sludge, forest industrial sludge, manure, Paper Wood Plastic, tyre, leather waste, cardboard rejects, meat and bone meal, liquid animal and vegetable wastes, tall oil pitch, peat, residues from food industry, biomal (including slaughterhouse waste) and lignin. The report includes two main chapters; a general risk chapter and a chapter of fuel specific risks. The first one deals with the general concept of risk, it highlights laws and rules relevant for risk management and it discuss general risks that are related to the different steps of fuel handling, i.e. unloading, storing, processing the fuel, transportation within the facility, combustion and handling of ashes. The information that was used to produce this chapter was gathered through a literature review, site visits, and the project group's experience from risk management. The other main chapter deals with fuel-specific risks and the measures to reduce the risks for the steps of unloading, storing, processing the fuel, internal transportation, combustion and handling of the ashes. Risks and measures were considered for all the biofuels included in the second version in the handbook of fuels. Information about the risks and risk management was gathered through interviews with people working with different kinds of fuels in electricity and heat plants in Sweden. The information from

  9. Seismic risk perception test

    Science.gov (United States)

    Crescimbene, Massimo; La Longa, Federica; Camassi, Romano; Pino, Nicola Alessandro

    2013-04-01

    The perception of risks involves the process of collecting, selecting and interpreting signals about uncertain impacts of events, activities or technologies. In the natural sciences the term risk seems to be clearly defined, it means the probability distribution of adverse effects, but the everyday use of risk has different connotations (Renn, 2008). The two terms, hazards and risks, are often used interchangeably by the public. Knowledge, experience, values, attitudes and feelings all influence the thinking and judgement of people about the seriousness and acceptability of risks. Within the social sciences however the terminology of 'risk perception' has become the conventional standard (Slovic, 1987). The mental models and other psychological mechanisms which people use to judge risks (such as cognitive heuristics and risk images) are internalized through social and cultural learning and constantly moderated (reinforced, modified, amplified or attenuated) by media reports, peer influences and other communication processes (Morgan et al., 2001). Yet, a theory of risk perception that offers an integrative, as well as empirically valid, approach to understanding and explaining risk perception is still missing". To understand the perception of risk is necessary to consider several areas: social, psychological, cultural, and their interactions. Among the various research in an international context on the perception of natural hazards, it seemed promising the approach with the method of semantic differential (Osgood, C.E., Suci, G., & Tannenbaum, P. 1957, The measurement of meaning. Urbana, IL: University of Illinois Press). The test on seismic risk perception has been constructed by the method of the semantic differential. To compare opposite adjectives or terms has been used a Likert's scale to seven point. The test consists of an informative part and six sections respectively dedicated to: hazard; vulnerability (home and workplace); exposed value (with reference to

  10. What is a risk. [Quantitative risk analysis

    Energy Technology Data Exchange (ETDEWEB)

    Schoen, G [Physikalisch-Technische Bundesanstalt, Braunschweig (Germany, F.R.)

    1979-02-01

    The following article is a revised version of a lecture given by the author during the VDE meeting 'Technical Expert Activities' in Brunswick. First of all, the concept of 'risk' is discussed which leads to a probability scale which then permits a definition of the 'justifiable risk' as the boundary between 'hazard' and 'safety'. The boundary is quantified indirectly from laws, regulations, instructions, etc. to the 'Technological rules' for special fields of application by minimum requirement data. These viewpoints described in detail are not only of substantial significance for the creation of safety regulations but also for their application and consequently for jurisdiction.

  11. Price Risk and Risk Management in Agriculture

    Directory of Open Access Journals (Sweden)

    Udo Broll

    2013-06-01

    Full Text Available This note studies the risk-management decisions of a risk-averse farmer. The farmer faces multiple sources of price uncertainty. He sells commodities to two markets at two prices, but only one of these markets has a futures market. We show that the farmer’s optimal commodity futures market position, i.e., a cross-hedge strategy, is actually an over-hedge, a full-hedge, or an under-hedge strategy, depending on whether the two prices are strongly positively correlated, uncorrelated, or negatively correlated, respectively.

  12. Nuclear safety research - risk and other risks

    International Nuclear Information System (INIS)

    Rossin, A.D.

    1982-01-01

    The nuclear power industry deals in many kinds of risks, complicated by political stress and communication problems. Power plant design must prepare for the unexpected attack, physical as well as psychological, but a zero-defects technology is not possible. The public has not been made sufficiently aware of the risk the US takes if there is not enough energy because nuclear power has been curtailed. Energy shortages could drive industry and jobs abroad, force the public to turn to government for a solution, drive the country to energy allocation, and cause a nuclear war. Policies that prevent closing the nuclear fuel cycle are ineffective in preventing proliferation and counterproductive to national needs

  13. 76 FR 1889 - Risk-Based Capital Guidelines: Market Risk

    Science.gov (United States)

    2011-01-11

    ... ``three-pillar'' framework that includes (i) risk-based capital requirements for credit risk, market risk... incremental risk capital requirement to capture default and credit quality migration risk for non... (advanced approaches rules) (collectively, the credit risk capital rules) \\8\\ by requiring any bank subject...

  14. Risks, risk assessment and risk competence in toxicology

    Science.gov (United States)

    Stahlmann, Ralf; Horvath, Aniko

    2015-01-01

    Understanding the toxic effects of xenobiotics requires sound knowledge of physiology and biochemistry. The often described lack of understanding pharmacology/toxicology is therefore primarily caused by the general absence of the necessary fundamental knowledge. Since toxic effects depend on exposure (or dosage) assessing the risks arising from toxic substances also requires quantitative reasoning. Typically public discussions nearly always neglect quantitative aspects and laypersons tend to disregard dose-effect-relationships. One of the main reasons for such disregard is the fact that exposures often occur at extremely low concentrations that can only be perceived intellectually but not by the human senses. However, thresholds in the low exposure range are often scientifically disputed. At the same time, ignorance towards known dangers is wide-spread. Thus, enhancing the risk competence of laypersons will have to be initially restricted to increasing the awareness of existing problems. PMID:26195922

  15. Risks, risk assessment and risk competence in toxicology.

    Science.gov (United States)

    Stahlmann, Ralf; Horvath, Aniko

    2015-01-01

    Understanding the toxic effects of xenobiotics requires sound knowledge of physiology and biochemistry. The often described lack of understanding pharmacology/toxicology is therefore primarily caused by the general absence of the necessary fundamental knowledge. Since toxic effects depend on exposure (or dosage) assessing the risks arising from toxic substances also requires quantitative reasoning. Typically public discussions nearly always neglect quantitative aspects and laypersons tend to disregard dose-effect-relationships. One of the main reasons for such disregard is the fact that exposures often occur at extremely low concentrations that can only be perceived intellectually but not by the human senses. However, thresholds in the low exposure range are often scientifically disputed. At the same time, ignorance towards known dangers is wide-spread. Thus, enhancing the risk competence of laypersons will have to be initially restricted to increasing the awareness of existing problems.

  16. Risks, risk assessment and risk competence in toxicology

    Directory of Open Access Journals (Sweden)

    Stahlmann, Ralf

    2015-07-01

    Full Text Available Understanding the toxic effects of xenobiotics requires sound knowledge of physiology and biochemistry. The often described lack of understanding pharmacology/toxicology is therefore primarily caused by the general absence of the necessary fundamental knowledge. Since toxic effects depend on exposure (or dosage assessing the risks arising from toxic substances also requires quantitative reasoning. Typically public discussions nearly always neglect quantitative aspects and laypersons tend to disregard dose-effect-relationships. One of the main reasons for such disregard is the fact that exposures often occur at extremely low concentrations that can only be perceived intellectually but not by the human senses. However, thresholds in the low exposure range are often scientifically disputed. At the same time, ignorance towards known dangers is wide-spread. Thus, enhancing the risk competence of laypersons will have to be initially restricted to increasing the awareness of existing problems.

  17. Ransomware: Minimizing the Risks.

    Science.gov (United States)

    Pope, Justin

    2016-01-01

    This ongoing column is dedicated to providing information to our readers on managing legal risks associated with medical practice. We invite questions from our readers. The answers are provided by PRMS, Inc. (www.prms.com), a manager of medical professional liability insurance programs with services that include risk management consultation, education and onsite risk management audits, and other resources to healthcare providers to help improve patient outcomes and reduce professional liability risk. The answers published in this column represent those of only one risk management consulting company. Other risk management consulting companies or insurance carriers may provide different advice, and readers should take this into consideration. The information in this column does not constitute legal advice. For legal advice, contact your personal attorney. Note: The information and recommendations in this article are applicable to physicians and other healthcare professionals so "clinician" is used to indicate all treatment team members.

  18. Risk assessment and regulation

    International Nuclear Information System (INIS)

    1981-01-01

    The approach to determining how safe is safe for the nuclear industry is to ensure that the risks are comparable with or less than those of other safe industries. There are some problems in implementing such an approach, because the effects of low levels of radiation are stochastic and assumptions are required in estimating the risks. A conservative approach has generally been adopted. Risk estimates across different activities are a useful indication of where society may be overspending or underspending to reduce risk, but the analysis has to take account of public preferences. Once risks have been estimated, limits may be chosen which the industry is expected to meet under normal and postulated accident conditions. Limits have been set so that nuclear risks do not exceed those in safe industries, and under normal conditions nuclear facilities operate at levels far below these specified limits

  19. Risk based modelling

    International Nuclear Information System (INIS)

    Chapman, O.J.V.; Baker, A.E.

    1993-01-01

    Risk based analysis is a tool becoming available to both engineers and managers to aid decision making concerning plant matters such as In-Service Inspection (ISI). In order to develop a risk based method, some form of Structural Reliability Risk Assessment (SRRA) needs to be performed to provide a probability of failure ranking for all sites around the plant. A Probabilistic Risk Assessment (PRA) can then be carried out to combine these possible events with the capability of plant safety systems and procedures, to establish the consequences of failure for the sites. In this way the probability of failures are converted into a risk based ranking which can be used to assist the process of deciding which sites should be included in an ISI programme. This paper reviews the technique and typical results of a risk based ranking assessment carried out for nuclear power plant pipework. (author)

  20. [Risk factors of schizophrenia].

    Science.gov (United States)

    Suvisaari, Jaana

    2010-01-01

    Schizophrenia is a multifactorial, neurodevelopmental disorder caused by a combination of genetic and environmental risk factors. Disturbances of brain development begin prenatally, while different environmental insults further affect postnatal brain maturation during childhood and adolescence. Genome-wide association studies (GWAS) have succeeded in identifying hundreds of new risk variants for common, multifactorial diseases. In schizophrenia research, GWAS have found several rare copy number variants that considerably increase the risk of schizophrenia, and have shown an association between schizophrenia and the major histocompatibility complex. Research on environmental risk factors in recent years has provided new information particularly on risk factors related to pregnancy and childhood rearing environment. Gene-environment interactions have become a central research topic. There is evidence that genetically susceptible children are more vulnerable to the effects of unstable childhood rearing environment and other environmental risk factors.

  1. Entrepreneurs Facing Risk

    DEFF Research Database (Denmark)

    Zichella, Giulio; Reichstein, Toke

    to choose risk vis-à-vis certainty. Drawing on prospect theory, we formulate hypotheses about the greater likelihood that entrepreneurs (compared to others) will choose risk immediately after a positive gain, but will shy away from risk compared to others as the degree of risk increases. The hypotheses......Theory conjectures that entrepreneurs are more likely than others to make risky choices. However, the empirical evidence is mixed. This paper offers new insights into entrepreneurs’ tendencies to make risky choices, by investigating the circumstances in which entrepreneurs are more/less likely...... are tested using data collected in laboratory-based real money games experiments. We find support for our hypotheses, indicating that entrepreneurs’ bias towards risk is circumstantial. These results have fundamental implications for our understanding of factors guiding entrepreneurial choices under risk...

  2. On risks and acceptability

    International Nuclear Information System (INIS)

    Watson, S.R.

    1981-01-01

    A very attractive notion is that it should be possible not only to determine how much risk is associated with any particular activity, but also to determine if that risk is acceptable. Stated boldly this seems an entirely unobjectionable and indeed a very acceptable notion. There is, however, underlying this idea, a mistaken view of risk which we might refer to as the ''phlogiston'' theory of risk. In this paper, presented at the SRP meeting on Ethical and Legal Aspects of Radiological Protection, the phlogiston theory of risk is described; secondly, it will be argued that it is too simple a theory to be realistic or useful; and thirdly, the management of risk will be placed in a wider decision framework. Acceptability, it will be argued is highly dependent on context, and it is not possible, therefore, to lay down generally applicable notions of acceptability. (author)

  3. The risk game

    International Nuclear Information System (INIS)

    Slovic, Paul

    1998-01-01

    In the context of health, safety, and environmental decisions, the concept of risk involves value judgments that reflect much more than just the probability and consequences of the occurrence of an event. This article conceptualizes the act of defining and assessing risk as a game, in which the rules must be socially negotiated within the context of a specific problem. This contextualist view of risk provides insight into why technical approaches to risk management often fail with problems such as those involving radiation and chemicals, where scientific experts and the public disagree on the nature of the risks. It also highlights the need for allowing the interested and affected parties to define and play the game, thus emphasizing the importance of institutional, procedural, and societal processes in risk-management decisions

  4. Patient caries risk assessment

    DEFF Research Database (Denmark)

    Twetman, Svante; Fontana, Margherita

    2009-01-01

    Risk assessment is an essential component in the decision-making process for the correct prevention and management of dental caries. Multiple risk factors and indicators have been proposed as targets in the assessment of risk of future disease, varying sometimes based on the age group at which...... they are targeted. Multiple reviews and systematic reviews are available in the literature on this topic. This chapter focusses primarily on results of reviews based on longitudinal studies required to establish the accuracy of caries risk assessment. These findings demonstrate that there is a strong body...... of evidence to support that caries experience is still, unfortunately, the single best predictor for future caries development. In young children, prediction models which include a variety of risk factors seem to increase the accuracy of the prediction, while the usefulness of additional risk factors...

  5. Ransomware: Minimizing the Risks

    OpenAIRE

    Pope, Justin

    2016-01-01

    This ongoing column is dedicated to providing information to our readers on managing legal risks associated with medical practice. We invite questions from our readers. The answers are provided by PRMS, Inc. (www.prms.com), a manager of medical professional liability insurance programs with services that include risk management consultation, education and onsite risk management audits, and other resources to healthcare providers to help improve patient outcomes and reduce professional liabili...

  6. State of risk assessment

    International Nuclear Information System (INIS)

    Conrad, J.

    1978-03-01

    In view of the growing importance assumed in recent years by scientific work on the calculation, quantification, evaluation and acceptance as well as behavior in the face of risks in general and more specifically, the risks of large industrial plants, the report attempts to provide a survey of the current situation, results and evaluation of this new branch of research, risk assessment. The emphasis of the report is on the basic discussion and criticism of the theoretical and methodological approaches used in the field of risk assessment (section 3). It is concerned above all with - methodical problems of determining and quantifying risks (3.1) - questions of the possibility of risk evaluation and comp arison (3.1, 3.2) - the premises of normative and empirical studies on decision making under risk (3.2, 3.3) - investigations into society's acceptance of risks involved in the introduction of new technologies (3.4) - attempts to combine various aspects of the field of risk assessment in a unified concept (3.5, 3.6, 3.7). Because risk assessment is embedded in the framework of decision theory and technology assessment, it can be implicitly evaluated at a more general level within this framework, as far as its possibilities and weaknesses of method and application are concerned (section 4). Sections 2 and 5 deal with the social context of origin and utilization of risk assessment. Finally, an attempt is made at a summary indicating the possible future development of risk assessment. (orig./HP) [de

  7. Risk evaluation for structures

    International Nuclear Information System (INIS)

    Freudenthal, A.M.; Schueller, G.I.

    1976-01-01

    The basic principles of the risk analysis, which is based on classical statistics is discussed. The significance of the Asymptotic (Extreme Value) distributions as well as the method of basing the level of acceptable risk on economical optimization procedures is pointed out. The application of the risk analysis to special type structures such as fixed offshore platforms, television towers, reactor containments and the reliability of reactor components under creep and fatigue load is elaborated by carrying out numerical examples. (orig./HP) [de

  8. Value of risk management

    OpenAIRE

    Vik, Marie Amdal

    2012-01-01

    Master's thesis in Risk management The overall aim of this study was to discuss the validity of the hypothesis that risk management contributes with added value to projects and the enterprise holding the projects, and consequently to the enterprise’s stakeholders. To examine this hypothesis, a case study of three projects taken from the same portfolio at Statoil was selected. The projects were said to have an active risk management. Data was collected from the project’s documentation as...

  9. On Modeling Risk Shocks

    OpenAIRE

    Dorofeenko, Victor; Lee, Gabriel; Salyer, Kevin; Strobel, Johannes

    2016-01-01

    Within the context of a financial accelerator model, we model time-varying uncertainty (i.e. risk shocks) through the use of a mixture Normal model with time variation in the weights applied to the underlying distributions characterizing entrepreneur productivity. Specifically, we model capital producers (i.e. the entrepreneurs) as either low-risk (relatively small second moment for productivity) and high-risk (relatively large second moment for productivity) and the fraction of both types is...

  10. Nuclear financial risk

    International Nuclear Information System (INIS)

    Heising, C.D.; George, V.P.

    1986-01-01

    This study examines the economy-wide financial risk associated with reactor accidents as a result of various regulatory response options that might be imposed after a serious accident, including partial or complete nuclear moratoria. The authors find that such risks may be two to three times greater than the plant-specific financial risk estimates that have previously been calculated by others (ie 500 million (1985) dollars per reactor year versus 5 to 50 million dollars). (author)

  11. Supply Cain Risk Management

    OpenAIRE

    Goodwin, Les

    2011-01-01

    “The management of supply chain risk is crucial to any business, more so to Rolls Royce who face an almost doubling of load within the next 10 years. So what is supply chain risk management and how well is it deployed within an operational business of Rolls Royce? What are the tools and techniques available and what are the key issues around implementing world class supply chain risk management with a Supply Chain Unit within Rolls Royce?”

  12. GM Risk Assessment

    Science.gov (United States)

    Sparrow, Penny A. C.

    GM risk assessments play an important role in the decision-making process surrounding the regulation, notification and permission to handle Genetically Modified Organisms (GMOs). Ultimately the role of a GM risk assessment will be to ensure the safe handling and containment of the GMO; and to assess any potential impacts on the environment and human health. A risk assessment should answer all ‘what if’ scenarios, based on scientific evidence.

  13. High-Risk List

    Science.gov (United States)

    2017-01-01

    economy. The World Bank has said that “corruption creates an unfavorable business environment by undermining the operation efficiency of firms and... Bank Began as ‘Ponzi Scheme,’” 11/27/2012. 64 Independent Joint Anti-Corruption Monitoring and Evaluation Committee, Unfinished Business : The Follow...HIGH RISK AREA 7: Oversight 51 HIGH-RISK AREA 8: Strategy and Planning 55 CONCLUSION HIGH RISK LIST I JANUARY 11, 2017 2 EXECUTIVE SUMMARY

  14. Supply chain risk management

    OpenAIRE

    Christian Hollstein; Frank Himpel

    2013-01-01

    Background: Supply chain risk management increasingly gains prominence in many international industries. In order to strengthen supply chain structures, processes, and networks, adequate potentials for risk management need to be built (focus on effective logistics) and to be utilized (focus on efficient logistics). Natural-based disasters, such as the case of Fukushima, illustrate how crucial risk management is. Method: By aligning a theoretical-conceptual framework with empirical-induct...

  15. Radiation risk estimation

    International Nuclear Information System (INIS)

    Schull, W.J.; Texas Univ., Houston, TX

    1992-01-01

    Estimation of the risk of cancer following exposure to ionizing radiation remains largely empirical, and models used to adduce risk incorporate few, if any, of the advances in molecular biology of a past decade or so. These facts compromise the estimation risk where the epidemiological data are weakest, namely, at low doses and dose rates. Without a better understanding of the molecular and cellular events ionizing radiation initiates or promotes, it seems unlikely that this situation will improve. Nor will the situation improve without further attention to the identification and quantitative estimation of the effects of those host and environmental factors that enhance or attenuate risk. (author)

  16. Risks: diagnosing and eliminating

    Directory of Open Access Journals (Sweden)

    Yuriy A. Tikhomirov

    2016-01-01

    Full Text Available Objective to develop conceptual theoretical and legal provisions and scientific recommendations on the identification analysis and elimination of risk. Methods universal dialectic method of cognition as well as scientific and private research methods based on it. Results the system was researched of risks diagnostics in the legal sphere and mechanism of influencing the quotrisk situationsquot and their consequences damage to the environment and harm to society. The concept of risk in the legal sphere was formulated the author39s classification of risks in the legal sphere is presented. The rules of analysis evaluation and prevention of risks and the model risk management framework are elaborated. Scientific novelty the mechanism for the identification analysis and elimination of risk has been developed and introduced into scientific circulation the author has proposed the classification and types of risks the reasons and the conditions promoting the risk occurrence. Practical significance the provisions and conclusions of the article can be used in the scientific lawmaking and lawenforcement activity as well as in the educational process of higher educational establishments. nbsp

  17. Air quality risk management.

    Science.gov (United States)

    Williams, Martin L

    2008-01-01

    Rather than attempt to provide a comprehensive account of air quality risk assessment, as might be found in a textbook or manual, this article discusses some issues that are of current importance in the United Kingdom and the rest of Europe, with special emphasis on risk assessment in the context of policy formulation, and emerging scientific knowledge. There are two pollutants of particular concern and that both pose challenges for risk assessment and policy, and they are particulate matter (PM) and ozone. The article describes some issues for health risk assessment and finally some forward-looking suggestions for future approaches to air quality management.

  18. Risks of energy sources

    International Nuclear Information System (INIS)

    Pop-Jordanov, J.; Pop-Jordanova, N.

    1989-09-01

    The paper is devoted to comparative health and environmental risks of different energy sources and their influence to public perception, social acceptability and decision-making. The technical heights of the risks, expressed in the number of fatalities of labor and public per unit energy output, from fossil, nuclear and renewable sources are analysed and compared. The complete energy cycle from mining to waste disposal, as well as the future trends, are taken into account. A comparison of the risks of different energy systems with the anticipated global and national energy shares by source is also presented. Furthermore, detailed studies of the non-technical dimensions of the energy risks are performed. Using a modified attitude-behaviour model, the cognitive structure underlying the positions towards different energy options is investigated. Estimating the diverse acting of the risk components, the consequent changes in the rank ordering of the energy sources are deduced. Finally, adding the psychological components nuclear reaches the highest place. In this respect, a unified multidimensional space for the representation of various technological risks is introduced. It affords a comparison of the risks not only by their technical height, but also by other characteristics (involuntary, fearfulness etc.). Finally, it was pointed out that in considering the risk characteristics and constraints, as well as the external fields, a system approach has to be used, taking into account the risks simultaneously with the benefits. 12 refs, 4 figs, 2 tabs

  19. Facing reality minimizes risk

    International Nuclear Information System (INIS)

    Gallagher, J.L.

    1992-01-01

    Companies that provide technology or project management involving a wise range of risks will increasingly find much more complex contractual relationships with their customers. This is due largely to the pressures exerted on those relationships by third parties. This paper explores the relationships between private contractors and their customers (frequently government agencies) and how risks affect those relationships. Perceptions of risk sometimes outweigh genuine risks, and the distinction between the two is often irrelevant. Media, site neighbors, adversaries, regulators, and national officials often tip the balance between reality and perception

  20. Ecological risk assessment

    National Research Council Canada - National Science Library

    Suter, Glenn W; Barnthouse, L. W. (Lawrence W)

    2007-01-01

    Ecological risk assessment is commonly applied to the regulation of chemicals, the remediation of contaminated sites, the monitoring of importation of exotic organisms, the management of watersheds...

  1. Motivation for risk sports

    OpenAIRE

    Hlava, Daniel

    2015-01-01

    Title: Motivation for risk sports Objectives: The aim of our thesis is to find out primary and secondary motives of athletes for the operation of high-risk sports and coming back to it. We also want to find out what is the starter for doing risk sports. Other questions are why athletes keep doing it and how perceive the potential risk. Methods: In our study, we chose qualitative investigation method and semistructured interview with eight respondents. For the interview, we drew up a list of q...

  2. Is risk analysis scientific?

    Science.gov (United States)

    Hansson, Sven Ove; Aven, Terje

    2014-07-01

    This article discusses to what extent risk analysis is scientific in view of a set of commonly used definitions and criteria. We consider scientific knowledge to be characterized by its subject matter, its success in developing the best available knowledge in its fields of study, and the epistemic norms and values that guide scientific investigations. We proceed to assess the field of risk analysis according to these criteria. For this purpose, we use a model for risk analysis in which science is used as a base for decision making on risks, which covers the five elements evidence, knowledge base, broad risk evaluation, managerial review and judgment, and the decision; and that relates these elements to the domains experts and decisionmakers, and to the domains fact-based or value-based. We conclude that risk analysis is a scientific field of study, when understood as consisting primarily of (i) knowledge about risk-related phenomena, processes, events, etc., and (ii) concepts, theories, frameworks, approaches, principles, methods and models to understand, assess, characterize, communicate, and manage risk, in general and for specific applications (the instrumental part). © 2014 Society for Risk Analysis.

  3. Certification and risk management

    International Nuclear Information System (INIS)

    Villanueva Fernandez, M.

    2015-01-01

    Nowadays more organizations are increasingly aware of the importance of properly managing the uncertainty of its activities and build competitive advantages through the identification, assessment and management of risks that they face. Risk management is also an aspect of great importance within the new version of ISO fact it is one of the most innovative and also the most laborious, because an appropriate risk management achieves expected results and customer satisfaction. In conclusion, risk management is a new field of business and can be considered a cross-cutting component for other relevant factors of organizational change management. (Author)

  4. Risk estimation and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ferguson, R A.D.

    1982-10-01

    Risk assessment involves subjectivity, which makes objective decision making difficult in the nuclear power debate. The author reviews the process and uncertainties of estimating risks as well as the potential for misinterpretation and misuse. Risk data from a variety of aspects cannot be summed because the significance of different risks is not comparable. A method for including political, social, moral, psychological, and economic factors, environmental impacts, catastrophes, and benefits in the evaluation process could involve a broad base of lay and technical consultants, who would explain and argue their evaluation positions. 15 references. (DCK)

  5. Risks in our society

    International Nuclear Information System (INIS)

    Cohen, B.L.

    1985-01-01

    This chapter summarizes quantitative information on risks from a wide variety of sources and analyzes it in terms of life expectancy reduction (LER). The data indicate that the greatest common risk in terms of LER, next to remaining unmarried, is cigarette smoking. When all of the effects of energy production and use (e.g., burning coal, reactor accidents) are totalled, the resulting LER is only about 25 days. It is pointed out that the risks to the residents of the Harrisburg area from radiation caused by the Three Mile Island accident is hundreds of thousands of times smaller than their risk from being overweight

  6. Approaches to acceptable risk

    International Nuclear Information System (INIS)

    Whipple, C.

    1997-01-01

    Several alternative approaches to address the question open-quotes How safe is safe enough?close quotes are reviewed and an attempt is made to apply the reasoning behind these approaches to the issue of acceptability of radiation exposures received in space. The approaches to the issue of the acceptability of technological risk described here are primarily analytical, and are drawn from examples in the management of environmental health risks. These include risk-based approaches, in which specific quantitative risk targets determine the acceptability of an activity, and cost-benefit and decision analysis, which generally focus on the estimation and evaluation of risks, benefits and costs, in a framework that balances these factors against each other. These analytical methods tend by their quantitative nature to emphasize the magnitude of risks, costs and alternatives, and to downplay other factors, especially those that are not easily expressed in quantitative terms, that affect acceptance or rejection of risk. Such other factors include the issues of risk perceptions and how and by whom risk decisions are made

  7. Mortgage Default Risk

    DEFF Research Database (Denmark)

    Chauvet, Marcelle; Gabriel, Stuart; Lutz, Chandler

    2016-01-01

    We use Google search query data to develop a broad-based and real-time index of mortgage default risk. Unlike established indicators, our Mortgage Default Risk Index (MDRI) directly reflects households’concerns regarding their risk of mortgage default. The MDRI predicts housing returns, mortgage ...... delinquency indicators, and subprime credit default swaps. These results persist both in- and out-of-sample and at multiple data frequencies. Together, research findings suggest internet search queries yield valuable new insights into household mortgage default risk....

  8. Agricultural risk management

    DEFF Research Database (Denmark)

    Lund, Mogens; Oksen, Arne; Larsen, Torben U.

    2005-01-01

    A new model for risk management in agriculture is described in the paper. The risk model is constructed as a context dependent process, which includes four main phases. The model is aimed at agricultural advisors, who wish to facilitate and disseminate risk management to farmers. It is developed...... and tested by an action research approach in an attempt to make risk management more applicable on family farms. Our obtained experiences indicate that farmers don’t apply probabilistic thinking and other concepts according to formal decision theory....

  9. Managing power risk

    International Nuclear Information System (INIS)

    Rudd, D.C.

    1999-01-01

    Issues regarding the management of financial risks in the electric power market were discussed. The nature of the risk was defined for electricity producers, local utilities, traders/dealers, and brokers, each of which are exposed to different types of risks with the exception of credit risk, which is common to all. The main features of options, swaps, CFDs, bilateral financial contracts, futures contracts and the terms of the NYMEX electricity contract were outlined. Basic derivative strategies, the role of the broker, the elements of emissions trading, and trading strategies for consumers were also explained. 3 fig

  10. General Concepts Regarding Risk Appetite

    OpenAIRE

    Ana-Maria Dinu

    2014-01-01

    Risk appetite is a very complex system, therefore one of the most important element of a company’s enterprise risk management (ERM) is the risk appetite defining. A proper risk management means making good choices towards the risks a company faces in order to achieve its objectives and measures to mitigate those risks, not to avoid them. Therefore, the moment risk appetite is understood and clearly defined can become a powerful tool both for managing the occurred risks and business performanc...

  11. Low Dose Risk, Decisions, and Risk Communication

    International Nuclear Information System (INIS)

    Flynn, James

    2002-01-01

    The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation

  12. Moral value, risk and risk tolerance

    International Nuclear Information System (INIS)

    Sjoeberg, L.; Drottz-Sjoeberg, B.M.

    1993-07-01

    In this paper, risk tolerance with regard to nuclear waste is investigated in two empirical studies. Earlier published data, based on home interviews, purporting to show that a majority of Swedes now would accept a local nuclear waste repository could not be replicated in a mail survey. Interviewer influence and implicit prompting were suggested as explanations of previous results, and a follow-up using implicit and explicit prompts showed that uncertain people were more likely to acquiesce in response to an implicit prompt. The acceptance of a local repository (measured as intention to vote in its favor in a local referendum) could not be well explained by a cost-benefit approach, neither by a risk perception model. Concern about the local community was an important determinant, however, and so were moral aspects. When these aspects were included in a model, about 60 per cent of the variance of risk perception and risk acceptance was accounted for. In further analyses, NIMBY respondents were identified, defined here as people who rejected a local repository in spite of having acknowledged substantial utility of nuclear power. NIMBYs were, however, only in a small minority of all opposition to a local repository. Cultural theory gave only a very small marginal level of explanation of perceived waste risk and acceptance. Few respondents stated that they would accept a local repository if they were to be given financial compensation. This fact may be related to nuclear power issues being conceived as general, rather than personal matters. Those who saw it as politically important also conceived of it in general rather than personal terms. 62 refs

  13. Are doctors risk takers?

    Directory of Open Access Journals (Sweden)

    Pikkel D

    2016-06-01

    Full Text Available Dvora Pikkel,1 Yael Sara Pikkel Igal,2 Adi Sharabi-Nov,3,4 Joseph Pikkel2,51Risk Management and Patient Safety Unit, Assuta Medical Center, Ramat Hahayal, Tel Aviv, 2Faculty of Medicine, Bar-Ilan University, 3Research Wing, Ziv Medical Center, Safed, 4Tel-Hai Academic College, Upper Galilee, 5Department of Ophthalmology, Ziv Medical Center, Safed, Israel Objective: Risk taking affects human behavior in general and decisions in medicine in particular. We used game theory to assess physicians' risk-taking tendencies. Methods: Physicians were recruited to the study by advertisement. It was explained that they would receive a sum of money for correct prediction of the flipping of a coin. They could try to sell their opportunity to flip the coin for an amount of money they determined. The sum offered by the participants was considered an indicator of risk taking. A demographic questionnaire assessed age, sex, seniority, and area of specialization of the participants. A multivariate analysis assessed associations between risk-taking behavior and, seniority, and specialization. Results: Sixty-two physicians participated, 36 males and 26 females, seniority 1–34 years. Of a possible range of 0–10, the mean score for risk taking was 5.5 – just slightly more than indifference. Negative correlations were found between risk taking and seniority, and between risk taking and age (β=–0.45, P<0.001 for both. Surgeons and anesthesiologists showed greater risk taking than did other physicians (β=0.69, P<0.05; and females less than males, though the latter correlation was not statistically significant. Conclusion: Understanding the tendency of physicians to risk taking may elucidate their decision-making processes and contribute to understanding of causes of adverse events and to the education of physicians. Keywords: risk taking, game theory, seniority, surgeons, anesthesiologists

  14. Risks from nuclear waste

    International Nuclear Information System (INIS)

    Liljenzin, J.O.; Rydberg, J.

    1996-11-01

    The first part of this review discusses the importance of risk. If there is any relation between the emotional and rational risk perceptions (for example, it is believed that increased knowledge will decrease emotions), it will be a desirable goal for society, and the nuclear industry in particular, to improve the understanding by the laymen of the rational risks from nuclear energy. This review surveys various paths to a more common comprehension - perhaps a consensus - of the nuclear waste risks. The second part discusses radioactivity as a risk factor and concludes that it has no relation in itself to risk, but must be connected to exposure leading to a dose risk, i.e. a health detriment, which is commonly expressed in terms of cancer induction rate. Dose-effect relations are discussed in light of recent scientific debate. The third part of the report describes a number of hazard indexes for nuclear waste found in the literature and distinguishes between absolute and relative risk scales. The absolute risks as well as the relative risks have changed over time due to changes in radiological and metabolic data and by changes in the mode of calculation. To judge from the literature, the risk discussion is huge, even when it is limited to nuclear waste. It would be very difficult to make a comprehensive review and extract the essentials from that. Therefore, we have chosen to select some publications, out of the over 100, which we summarize rather comprehensively; in some cases we also include our remarks. 110 refs, 22 figs

  15. Radiological risk comparison guidelines

    International Nuclear Information System (INIS)

    Hallinan, E.J.; Muhlestein, L.D.; Brown, L.F.; Yoder, R.E.

    1992-01-01

    An important aspect of DOE safety analyses is estimating potential accident risk. The estimates are used to: determine if additional controls are needed, identify Safety Class Items, and demonstrate adequate risk reduction. Thus, guidelines are needed to measure comparative risks. The Westinghouse M ampersand O Nuclear Facility Safety Committee and the Safety Envelope Working Group have developed radiological risk guidelines for comparing the risks from individual accident analyses. These guidelines were prepared under contract with the US Department of Energy. These guidelines are based on historical DOE guidelines and current requirements, and satisfy DOE and technical community proposals. for goals that demonstrate acceptable risk. The guidelines consist of a frequency versus consequence curve for credible accidents. Offsite and onsite guidelines are presented. The offsite risk acceptance guidelines are presented in Figure 1. The guidelines are nearly isorisk for anticipated events where impacts are chronic, and provide additional reduction for unlikely events where impacts may be acute and risk uncertainties may be significant. The guidelines are applied to individual release accident scenarios where a discrete frequency and consequence has been estimated. The guideline curves are not to be used for total risk assessments. Common cause events are taken into consideration only for an individual facility. Frequencies outside the guideline range are considered to be local site option (analyst judgement) as far as assessments of risk acceptance are concerned. If the curve is exceeded, then options include either a more detailed analysis or imposing additional preventive or mitigative features. Another presentation discusses implementation in detail. Additional work is needed to provide risk comparison guidelines for releases from multiple facilities and for toxic releases

  16. Risks from nuclear waste

    Energy Technology Data Exchange (ETDEWEB)

    Liljenzin, J.O.; Rydberg, J. [Radiochemistry Consultant Group, Vaestra Froelunda (Sweden)

    1996-11-01

    The first part of this review discusses the importance of risk. If there is any relation between the emotional and rational risk perceptions (for example, it is believed that increased knowledge will decrease emotions), it will be a desirable goal for society, and the nuclear industry in particular, to improve the understanding by the laymen of the rational risks from nuclear energy. This review surveys various paths to a more common comprehension - perhaps a consensus - of the nuclear waste risks. The second part discusses radioactivity as a risk factor and concludes that it has no relation in itself to risk, but must be connected to exposure leading to a dose risk, i.e. a health detriment, which is commonly expressed in terms of cancer induction rate. Dose-effect relations are discussed in light of recent scientific debate. The third part of the report describes a number of hazard indexes for nuclear waste found in the literature and distinguishes between absolute and relative risk scales. The absolute risks as well as the relative risks have changed over time due to changes in radiological and metabolic data and by changes in the mode of calculation. To judge from the literature, the risk discussion is huge, even when it is limited to nuclear waste. It would be very difficult to make a comprehensive review and extract the essentials from that. Therefore, we have chosen to select some publications, out of the over 100, which we summarize rather comprehensively; in some cases we also include our remarks. 110 refs, 22 figs.

  17. Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities.

    Directory of Open Access Journals (Sweden)

    Hanna Johansson

    Full Text Available Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic in predicting future development of high-grade cervical intraepithelial neoplasia (CIN among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS or low-grade squamous epithelial lesion (LSIL cytology.Archived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211 or LSIL, (n = 131 were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+.Twenty-nine percent (61/211 of the women in the ASCUS group, and 34.3% (45/131 in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0% (95% CI 85.9-94.0 among women with ASCUS and 95.4% (95% CI 91.8-99.0 among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02. The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95% CI 82.2-100, respectively and LSIL (97.8%, 95% CI 86.8-99.9 and 100%, 95% CI 79.9-100, respectively. The corresponding specificity was low, 12.7% (95% CI 7.9-19.3 and 5.8% (95% CI 2.2-13.6, for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27 as compared to 13.6% (43/315 of the mRNA-positive women (p = 0.03.The APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had high negative predictive value for future

  18. Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities

    Science.gov (United States)

    Johansson, Hanna; Bjelkenkrantz, Kaj; Darlin, Lotten; Dilllner, Joakim; Forslund, Ola

    2015-01-01

    Objective Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology. Methods Archived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211) or LSIL, (n = 131) were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+. Results Twenty-nine percent (61/211) of the women in the ASCUS group, and 34.3% (45/131) in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0% (95% CI 85.9-94.0) among women with ASCUS and 95.4% (95% CI 91.8-99.0) among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02). The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95% CI 82.2-100, respectively) and LSIL (97.8%, 95% CI 86.8-99.9 and 100%, 95% CI 79.9-100, respectively). The corresponding specificity was low, 12.7% (95% CI 7.9-19.3) and 5.8% (95% CI 2.2-13.6), for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27) as compared to 13.6% (43/315) of the mRNA-positive women (p = 0.03). Conclusion The APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had

  19. Risk and Derivative Price

    OpenAIRE

    Yusuke Osaki

    2007-01-01

    We consider an asset market traded three types of assets: the risk–free asset, the market portfolio and derivatives written on the market portfolio return. We determine a sufficient condition to guarantee that noise risk monotonically changes their derivatives. The condition is that Arrow–Pratt absolute risk aversion is decreasing and convex.

  20. Risk Aversion and Emotions

    NARCIS (Netherlands)

    Nguyen, Y.; Noussair, C.N.

    2013-01-01

    Abstract: We consider the relationship between emotions and decision-making under risk. Specifically, we examine the emotional correlates of risk-averse decisions. In our experiment, individuals' facial expressions are monitored with facereading software, as they are presented with risky lotteries.

  1. Commodity risk management

    Directory of Open Access Journals (Sweden)

    Hilary Till

    2016-09-01

    Full Text Available This article discusses the practical issues involved in applying a disciplined risk management methodology to commodity futures trading. Accordingly, the paper shows how to apply methodologies derived from both conventional asset management and hedge fund management to futures trading. The article also discusses some of the risk management issues that are unique to leveraged futures trading.

  2. [Prevention of psychosocial risks].

    Science.gov (United States)

    Dalle, Édouard; Trichard-Salembier, Alexandra; Sobaszek, Annie

    2018-02-01

    The theme of psychosocial risks remains in the workplace. It is therefore essential that all members of a company are made aware of the terminology and specific prevention actions in this field. Distinguishing between the manifestations of these risks and their causes and consequences helps to improve prevention. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Nanocosmetics: benefits and risks

    OpenAIRE

    Shokri, Javad

    2017-01-01

    Summary Various nanomaterials/nanoparticles (NPs) have been used for the development of cosmetic products - a field so-called nanocosmetic formulations. These advanced materials offer some benefits, while their utilization in the cosmetic formulations may be associated with some risks. The main aim of this editorial is to highlight the benefits and risks of the nanomaterials used in the cosmetic products.

  4. Perception of Product Risks

    NARCIS (Netherlands)

    Fischer, A.R.H.

    2017-01-01

    This chapter provides several explanations for consumer risk perception. For frequently repeated behavior that is seemingly under their own control, consumers tend to be overly optimistic. This occurs in spite of the general tendency of consumers to be risk averse. Specific dimensions of different

  5. Risk and response

    Energy Technology Data Exchange (ETDEWEB)

    Warner, F [Cremer and Warner (UK)

    1981-01-01

    A discussion of nuclear power and public acceptability can quite properly begin with a general consideration of the nature of response to risk. Response follows perception, and builds up from the individual through group response to the judgement of society expressed in governmental decisions on what is acceptable. Various types of risk, and public reaction, are discussed.

  6. Quantifying IT estimation risks

    NARCIS (Netherlands)

    Kulk, G.P.; Peters, R.J.; Verhoef, C.

    2009-01-01

    A statistical method is proposed for quantifying the impact of factors that influence the quality of the estimation of costs for IT-enabled business projects. We call these factors risk drivers as they influence the risk of the misestimation of project costs. The method can effortlessly be

  7. Information Security Risk Analysis

    CERN Document Server

    Peltier, Thomas R

    2010-01-01

    Offers readers with the knowledge and the skill-set needed to achieve a highly effective risk analysis assessment. This title demonstrates how to identify threats and then determine if those threats pose a real risk. It is suitable for industry and academia professionals.

  8. Melanoma Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  9. Social Discounting under Risk.

    Science.gov (United States)

    Jin, Jia; Pei, Guanxiong; Ma, Qingguo

    2017-01-01

    As a measure of how prosocial behavior depends on social distance, social discounting is defined as the decrease in generosity between the decision maker and the recipient as the social distance increases. While risk is a ubiquitous part of modern life, there is limited research on the relationship between risk and prosocial behavior. In the present experiment, we empirically test whether risk has an influence on social discounting. We use the choice titration procedure to examine this effect. Our data show that independent of risk, participants are less eager to forego money and exhibit more selfishness toward a specific person when the social distance increases; these findings are reflected in the hyperbolic model. Interestingly, risk influences the shape of the social discounting function, which is reflected in the notable different discount rates. Individuals who make decisions under risk yield a smaller discount rate than those who make decisions without risk, i.e., under risk subjects reduce less their generosity as a function of the social distance. Furthermore, this distinct type of generosity occurs typically among individuals with 10-distance recipients but not with the closest- and furthest-social-distance recipients.

  10. Reanalysis of Zion risk

    International Nuclear Information System (INIS)

    Park, C.K.; Unwin, S.D.; Cazzoli, E.; Tingle, A.; Chun, M.

    1988-01-01

    As part of the NUREG-1150 effort, Brookhaven National Laboratory (BNL) has undertaken a risk analysis of Zion Unit 1 adopting the methodology developed at Sandia National Laboratories (SNL) under the Severe Accident Risk Rebaselining Program. Resulting of the preliminary version of that analysis are reported here. Completion plans for the Zion study are described also

  11. Sovereign default risk assessment

    NARCIS (Netherlands)

    Rijken, H.A.; Altman, E.I.

    2013-01-01

    We propose a new approach toward assessing sovereign risk by examining rigorously the health and aggregate default risk of a nation's private corporate sector. Models can be utilised to measure the probability of default of the non-financial sector cumulatively for five years, both as an absolute

  12. Measuring Normative Risk Preferences

    NARCIS (Netherlands)

    G.A.G. Alserda (Gosse)

    2017-01-01

    textabstractThe results of eliciting risk preferences depend on the elicitation method. Different methods of measuring the same variable tend to produce different results. This raises the question whether normative risk preferences can be elicited at all. Using two types of manipulation, I assess

  13. Chemical Risk Assessment

    Science.gov (United States)

    This course is aimed at providing an overview of the fundamental guiding principles and general methods used in chemical risk assessment. Chemical risk assessment is a complex and ever-evolving process. These principles and methods have been organized by the National Research Cou...

  14. Environments at risk

    International Nuclear Information System (INIS)

    Ellis, D.

    1989-01-01

    The book is a product of the Canadian story in environmental management. Since the late 1960s the Canadian governments have reflected the growing environmental conscience and legislated many environmental controls. It is shown what has been achieved worldwide in environmental assessment an risk prediction. The 12 chapters include working concepts and examples for assessments, reducing risk, and self-help. (DG)

  15. Realized Volatility Risk

    NARCIS (Netherlands)

    D.E. Allen (David); M.J. McAleer (Michael); M. Scharth (Marcel)

    2013-01-01

    textabstractIn this paper we document that realized variation measures constructed from highfrequency returns reveal a large degree of volatility risk in stock and index returns, where we characterize volatility risk by the extent to which forecasting errors in realized volatility are substantive.

  16. Asymmetric Realized Volatility Risk

    NARCIS (Netherlands)

    D.E. Allen (David); M.J. McAleer (Michael); M. Scharth (Marcel)

    2014-01-01

    markdownabstract__Abstract__ In this paper we document that realized variation measures constructed from high-frequency returns reveal a large degree of volatility risk in stock and index returns, where we characterize volatility risk by the extent to which forecasting errors in realized

  17. Risks of Leveraged Products

    NARCIS (Netherlands)

    A. Di Cesare (Antonio)

    2012-01-01

    textabstractLeveraged investments have become a fundamental feature of modern economies. The new financial products allow people to take greater-than-usual exposures to risk factors. This thesis analyzes several different aspects of the risks involved by some frequently used leveraged products:

  18. Risk in social science

    National Research Council Canada - National Science Library

    Zinn, Jens; Taylor-Gooby, Peter

    2006-01-01

    ... for control. Advances in social science improve understanding of how people perceive and prioritise risks, broaden awareness of the bearing of a range of other issues (trust, experience during the life course, democratic expectations) on people's capacity to manage risks, and facilitate exploration of the ways in which people communicate abo...

  19. ORGANIZATIONAL RISK COMMUNICATION

    Science.gov (United States)

    Ris communication tools in organizations differs in several ways from many of tools and techniques developed for public meetings. The traditional view of risk communication seeks to manage the public outrage ssociated with site-based issues. Organizational risk communication seek...

  20. Mind Your Risks

    Science.gov (United States)

    ... ZIP 223KB Social Media Graphics Download .ZIP 293KB Social Media Graphics CAMPAIGN RESOURCES: SOCIAL MEDIA GRAPHICS Mind Your Risks® (MYR) ... ZIP 360KB Social Media Graphics Download .ZIP 433KB Social Media Graphics CAMPAIGN RESOURCES: SOCIAL MEDIA GRAPHICS Mind Your Risks® (MYR) ...

  1. Perspectives: Intellectual Risk Management

    Science.gov (United States)

    Hall, James C.

    2013-01-01

    Ask a college administrator about students and risk management, and you're likely to get a quick and agitated speech about alcohol consumption and bad behavior or a meditation on mental health and campus safety. But in colleges and universities, we manage intellectual risk-taking too. Bring that up, and you'll probably get little out of that same…

  2. Risk Management and Simulation

    DEFF Research Database (Denmark)

    Skovmand, David

    2014-01-01

    Review of: Risk Management and Simulation / Aparna Gupta. Boca Raton, FL: CRC Press, 2013, xxix + 491 pp., $99.95(H), ISBN: 978-1-4398-3594-4.......Review of: Risk Management and Simulation / Aparna Gupta. Boca Raton, FL: CRC Press, 2013, xxix + 491 pp., $99.95(H), ISBN: 978-1-4398-3594-4....

  3. Taming agricultural risks

    OpenAIRE

    Oppedahl, David B.

    2014-01-01

    On November 19, 2013, the Federal Reserve Bank of Chicago held a conference to explore the key risks faced by agricultural producers and lenders, as well as the risk-management tools available to them, in today’s volatile environment.

  4. Probabilistic risk assessment as an aid to risk management

    International Nuclear Information System (INIS)

    Garrick, B.J.

    1982-01-01

    Probabilistic risk assessments are providing important insights into nuclear power plant safety. Their value is two-fold: first as a means of quantifying nuclear plant risk including contributors to risk, and second as an aid to risk management. A risk assessment provides an analytical plant model that can be the basis for performing meaningful decision analyses for controlling safety. It is the aspect of quantitative risk management that makes probabilistic risk assessment an important technical discipline of the future

  5. Risks from radon

    International Nuclear Information System (INIS)

    Doll, Richard

    1992-01-01

    The best estimate of risk to which everyone is exposed from natural radon in buildings is now obtained by extrapolation from observations on men exposed to radon in mines. The relationship between dose and effect derived by the US National Research Council implies that about 6% of the current life-time risk of developing the disease in the UK is attributable to radon, but for residents of some houses it will be much greater. This estimate is dependent on many assumptions, some of which are certainly wrong, and reliable estimates can be obtained only by direct observations on people living in different houses. It is possible that radon may also cause some risk of other cancers, notably leukaemia, but such risks, if real, are certainly small. Studies in progress should provide reliable estimates of all radon induced risks within a few years. (author)

  6. Insurance against nuclear risks

    International Nuclear Information System (INIS)

    Dow, J.C.

    1976-01-01

    Virtually any type of nuclear risk is insurable in principle, providing, of course, that the necessary standards of safety and control are met. Some of the risks are of a relatively minor character and no more hazardous than a simple conventional risk. But insurers would not consider as a minor risk anything which involves the use of nuclear fuel or other nuclear materials which are in a critical state or capable of releasing dangerous levels of radioactivity. These would include nuclear reactors or, indeed, any type of assembly which can not be regarded as subcritical. Most insurers would also regard installations involved in the manufacturing, processing and enriching of nuclear fuel, and certainly those concerned with the reprocessing of irradiated fuel and plutonium extraction, as major risks. (HP) [de

  7. Risks in nuclear engineering

    International Nuclear Information System (INIS)

    Lindackers, K.H.

    1982-01-01

    The German nuclear power plant risk assessment study has not contributed to a higher degree of acceptance of light-water reactors among the general public. One reason is the fact that its predictions are much too inaccurate, and the consequences from severe accidents, regardless of their possibly extremely small likelihood, speak for themselves. The work still to be done in Phase B of the risk analysis will only be useful, if the safety factors in risk assessments can be drastically increased. The results of the risk analysis cannot be used in legislation or the administration of justice, because they are too incomplete and inaccurate. Scientific findings in risk analysis show that new designs and new components complicate objective judgement of changes in reactor safety engineering considerably. Every change in the required precautionary safety measures must be carefully considered, and if need be tested under the appropriate conditions. (orig./HSCH) [de

  8. EMF and risk perception

    International Nuclear Information System (INIS)

    Widemann, P.M.; Schuetz, H.

    1995-01-01

    There has lately been a greater responsivement in the media as well as the general public to the risk potential of high-frequency electromagnetic fields (EMF). If the discussion continues to gain momentum, this could have grave consequences for companies offering the products or services under attack. The working group Man, Environment, Technology (MUT) at Juelich Research Centre has examined the question of how EMF risks are valuated by the public. The study centered on the following questions: How are EMF risk potentials perceived by the public and what factors influence the public discussion? What future course might the discussion on risks take and what critical events and conditions deserve particular attention? The authors present and discuss the results of this first German study on product-inherent risks. (orig.) [de

  9. Risk capital allocation

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Smilgins, Aleksandrs

    Risk capital allocation problems have been widely discussed in the academic literature. We consider a company with multiple subunits having individual portfolios. Hence, when portfolios of subunits are merged, a diversification benefit arises: the risk of the company as a whole is smaller than...... the sum of the risks of the individual sub-units. The question is how to allocate the risk capital of the company among the subunits in a fair way. In this paper we propose to use the Lorenz set as an allocation method. We show that the Lorenz set is operational and coherent. Moreover, we propose a set...... of new axioms related directly to the problem of risk capital allocation and show that the Lorenz set satisfies these new axioms in contrast to other well-known coherent methods. Finally, we discuss how to deal with non-uniqueness of the Lorenz set....

  10. Fear, anger, and risk.

    Science.gov (United States)

    Lerner, J S; Keltner, D

    2001-07-01

    Drawing on an appraisal-tendency framework (J. S. Lerner & D. Keltner, 2000), the authors predicted and found that fear and anger have opposite effects on risk perception. Whereas fearful people expressed pessimistic risk estimates and risk-averse choices, angry people expressed optimistic risk estimates and risk-seeking choices. These opposing patterns emerged for naturally occurring and experimentally induced fear and anger. Moreover, estimates of angry people more closely resembled those of happy people than those of fearful people. Consistent with predictions, appraisal tendencies accounted for these effects: Appraisals of certainty and control moderated and (in the case of control) mediated the emotion effects. As a complement to studies that link affective valence to judgment outcomes, the present studies highlight multiple benefits of studying specific emotions.

  11. Mapping of nitrogen risks

    DEFF Research Database (Denmark)

    Blicher-Mathiesen, Gitte; Andersen, Hans Estrup; Carstensen, Jacob

    2014-01-01

    risk mapping part of the tool, we combined a modelled root zone N leaching with a catchment-specific N reduction factor which in combination determines the N load to the marine recipient. N leaching was calculated using detailed information of agricultural management from national databases as well...... will be more effective if they are implemented in N loss hot spots or risk areas. Additionally, the highly variable N reduction in groundwater and surface waters needs to be taken into account as this strongly influences the resulting effect of mitigation measures. The objectives of this study were to develop...... and apply an N risk tool to the entire agricultural land area in Denmark. The purpose of the tool is to identify high risk areas, i.e. areas which contribute disproportionately much to diffuse N losses to the marine recipient, and to suggest cost-effective measures to reduce losses from risk areas. In the N...

  12. WHO risk communication seminar

    International Nuclear Information System (INIS)

    1998-01-01

    The International EMF project organised by the WHO is now entering its third year. In addition to providing authoritative reviews of the scientific literature on the health effects of exposure to electric and magnetic fields, a key objective of the five year programme is to provide information on the perception, communication and management of risk, and how this relates to electric and magnetic fields. To this end, an International seminar on: Risk perception, risk communication and its application to EMF exposure, was held in Vienna on 22-23 October last year, bringing togehter an array of speakers from around the world to talk about perceptions of risk, how best to communicate risks to the public and present some practical examples. (author)

  13. Managing Risk and Opportunity

    DEFF Research Database (Denmark)

    Andersen, Torben Juul; Garvey, Maxine; Roggi, Oliviero

    outcomes. This topic is timely and of interest both to the academic community as well as to practicing managers, executives, and directors. The volume focuses on contemporary risk leadership issues based on recent research insights but avoids excessive technical language and mathematical formulas. The book...... is framed around the challenges imposed on executives and directors in dealing with an increasingly complex and unpredictable world. This requires a new risk leadership focus that not only avoids the downside risks but also considers ways to exploit the upside potential offered by a dynamic environment....... The underlying logic is built on the principles of financial economics where benefits derive from reducing bankruptcy costs and increasing future cash inflows. This provides a stringent framework for analyzing the effect of different risk management actions and behaviors in effective risk-taking organizations...

  14. Judging risk behaviour and risk preference: the role of the evaluative connotation of risk terms.

    NARCIS (Netherlands)

    van Schie, E.C.M.; van der Pligt, J.; van Baaren, K.

    1993-01-01

    Two experiments investigated the impact of the evaluative connotation of risk terms on the judgment of risk behavior and on risk preference. Exp 1 focused on the evaluation congruence of the risk terms with a general risk norm and with Ss' individual risk preference, and its effects on the extremity

  15. LOW DOSE RISK, DECISIONS, and RISK COMMUNICATION

    International Nuclear Information System (INIS)

    Flynn, James

    2002-01-01

    The objective of this project is to conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low-dose exposures. Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low-dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

  16. Induction of human papilloma virus E6/E7-specific cytotoxic T-lymphocyte activity in immune-tolerant, E6/E7-transgenic mic

    NARCIS (Netherlands)

    Riezebos-Brilman, A; Regts, J; Freyschmidt, EJ; Dontje, B; Wilschut, J; Daemen, T

    Despite promising preclinical results of various therapeutic anticancer immunization strategies, these approaches may not be effective enough to eradicate tumors in cancer patients. While most animal models are based on fast-growing transplantable tumors, malignancies in, for example, cervical

  17. Communication of Audit Risk to Students.

    Science.gov (United States)

    Alderman, C. Wayne; Thompson, James H.

    1986-01-01

    This article focuses on audit risk by examining it in terms of its components: inherent risk, control risk, and detection risk. Discusses applying audit risk, a definition of audit risk, and components of audit risk. (CT)

  18. Internal Audit and Risk Management

    OpenAIRE

    Constantin Nicolae Vasile; Alexandru Georgiana

    2011-01-01

    Internal audit and risk management have the same goal: the control of risk. There are various roles for the internal audit in respect of risk management. The main limitations of internal audit in respect of risk management regards assuming risk management tasks. One of the main issues regarding risk management is to make sure that the key risks are taken into consideration and that the management and the board of the organization take action as needed. Internal audit could give advice to mana...

  19. Society's general exposure to risk

    International Nuclear Information System (INIS)

    Lidstone, R.F.

    1981-10-01

    Canadian and world experience with accidents and disease is reviewed in order to identify risk information that might extend the societal perspective on health risk beyond daily concerns. The level of exposure to catastrophic risks is compared to that associated with commonly experienced risks. An examination of current and historical levels of Canadian mortality risk is included. The association between mortality risk and Canadian industrial activity is also examined. Some prospects for utilizing these risk benchmarks are then discussed

  20. Coastal risk forecast system

    Science.gov (United States)

    Sabino, André; Poseiro, Pedro; Rodrigues, Armanda; Reis, Maria Teresa; Fortes, Conceição J.; Reis, Rui; Araújo, João

    2018-03-01

    The run-up and overtopping by sea waves are two of the main processes that threaten coastal structures, leading to flooding, destruction of both property and the environment, and harm to people. To build early warning systems, the consequences and associated risks in the affected areas must be evaluated. It is also important to understand how these two types of spatial information integrate with sensor data sources and the risk assessment methodology. This paper describes the relationship between consequences and risk maps, their role in risk management and how the HIDRALERTA system integrates both aspects in its risk methodology. It describes a case study for Praia da Vitória Port, Terceira Island, Azores, Portugal, showing that the main innovations in this system are twofold: it represents the overtopping flow and consequent flooding, which are critical for coastal and port areas protected by maritime structures, and it works also as a risk assessment tool, extremely important for long-term planning and decision-making. Moreover, the implementation of the system considers possible known variability issues, enabling changes in its behaviour as needs arise. This system has the potential to become a useful tool for the management of coastal and port areas, due to its capacity to effectively issue warnings and assess risks.

  1. Country risk analysis

    International Nuclear Information System (INIS)

    David, A.

    1992-01-01

    This paper reports that the oil industry has been an internationally based industry that has been heavily dependent on outside financing sources. Historically, financing came from investment houses that, in most cases, participated in the projects as equity investors. However, investment companies can no longer satisfy the capital requirements of the current high level of exploration and development activities. The current trend is to involve commercial banks on a purely lending basis. Commercial banks, by their nature, are risk averse. In the case of oil and gas exploration and production they are asked to take not only technical risk and price risk but geopolitical risk as well. Methods have been developed by commercial banks to reduce technical and price risks to point which enables them to be comfortable with a loan. However, geopolitical risks are more difficult to assess. The risk associated with many countries are the nationalization of the investment, new tax restrictions, restriction of currency movements, and/or revisions to the production sharing agreements

  2. Coastal risk forecast system

    Science.gov (United States)

    Sabino, André; Poseiro, Pedro; Rodrigues, Armanda; Reis, Maria Teresa; Fortes, Conceição J.; Reis, Rui; Araújo, João

    2018-04-01

    The run-up and overtopping by sea waves are two of the main processes that threaten coastal structures, leading to flooding, destruction of both property and the environment, and harm to people. To build early warning systems, the consequences and associated risks in the affected areas must be evaluated. It is also important to understand how these two types of spatial information integrate with sensor data sources and the risk assessment methodology. This paper describes the relationship between consequences and risk maps, their role in risk management and how the HIDRALERTA system integrates both aspects in its risk methodology. It describes a case study for Praia da Vitória Port, Terceira Island, Azores, Portugal, showing that the main innovations in this system are twofold: it represents the overtopping flow and consequent flooding, which are critical for coastal and port areas protected by maritime structures, and it works also as a risk assessment tool, extremely important for long-term planning and decision-making. Moreover, the implementation of the system considers possible known variability issues, enabling changes in its behaviour as needs arise. This system has the potential to become a useful tool for the management of coastal and port areas, due to its capacity to effectively issue warnings and assess risks.

  3. The risks of technology

    International Nuclear Information System (INIS)

    Hauptmanns, U.; Werner, W.; Herttrich, M.

    1987-01-01

    The book presents a complete survey of the methods and procedures applied for risk assessment, referring in particular to the field of nuclear engineering, but dealing also with risk assessment in the sector of the chemical industry and of the power industry, comparing the risks of various technologies for energy production. The material presented shows that a risk assessment study requires information and knowledge from a great variety of subject fields, evaluating and merging the information collected into a complete survey being the main task of risk assessment. It also becomes clear that despite the strong commitment to research in this field, there still remain unresolved problems and phenomena, so that risk assessment bears a certain degree of uncertainty. The results and the mutual connections are represented in words only, so that the reader can do without mathematical knowledge. Many studies and their results are presented, and their explanation in the overall framework allows insight into the connections and an evaluation of usefulness. The status report on risk assessment prepared in August 1984 by the GRS (Society for Reactor Safety) on behalf of the Federal Ministry of the Interior, has been taken as a basis for this book which consists of many individual contributions. (orig./HP) With 45 figs [de

  4. Risk perception in planning

    Energy Technology Data Exchange (ETDEWEB)

    Roh, S K

    1987-01-01

    The general public's perception of the risks involved with hazardous industries is increasing, especially in countries that high environmental amenity characteristics. This increased public awareness of risk may be an important factor in the future of countries who produce a large quantity of petroleum and chemical products. However, existing decision-making processes for determining safety controls do not take sufficient account of the community perception of risk. Identification of perceived risk levels could contribute to the determination of safe land-use planning policies and practices. The objective of land-use planning for hazardous industries is to reduce the gap between the calculated or technical assessment of risk and the risk as perceived by the community. This also facilitates a balanced approach in the decision making process between meeting industry requirements and community concerns. The comprehensive analysis presented in this study, based on a questionnaire given to residents in each of the three study areas (Australia, Japan and Korea), focused on identifying and measuring the respondent's understanding of the risk posed by nearby hazardous industrial developments.

  5. Introduction: Learning about Risk

    Directory of Open Access Journals (Sweden)

    Jens O. Zinn

    2006-01-01

    Full Text Available The special issue "Learning about Risk" draws on the launch conference of the ESRC "Social Contexts and Responses to Risk" network (SCARR held at 28th – 29th January 2005 in Canterbury. The SCARR network is an interdisciplinary network on risk which examines perceptions of and responses to risk in a range of areas, including sexual behaviour and partnering choices, the mass media, faith and ethnicity, pensions and financial planning, industrial pollution, crime, transport, energy policy and environmental hazards. The network's launch conference reflected the interdisciplinary character of risk research including a range of different methods and approaches to risk, directed at diverse objects of interest. The idea of the special issue is to link together this diversity and interdisciplinarity in risk research, and to encourage perspectives that look beyond the boundaries of single disciplines and methodological approaches. The papers in this publication demonstrate the value of insights from different disciplinary backgrounds in this area and point to the opportunities and challenges in the work that remains to be done in drawing these several perspectives more closely together. URN: urn:nbn:de:0114-fqs0601246

  6. 77 FR 53059 - Risk-Based Capital Guidelines: Market Risk

    Science.gov (United States)

    2012-08-30

    ...'' framework that includes (1) Risk-based capital requirements for credit risk, market risk, and operational... default and credit quality migration risk for non-securitization credit products. With respect to... securitization positions, the revisions assign a specific risk- weighting factor based on the credit rating of a...

  7. Contralateral breast cancer risk

    International Nuclear Information System (INIS)

    Unnithan, Jaya; Macklis, Roger M.

    2001-01-01

    The use of breast-conserving treatment approaches for breast cancer has now become a standard option for early stage disease. Numerous randomized studies have shown medical equivalence when mastectomy is compared to lumpectomy followed by radiotherapy for the local management of this common problem. With an increased emphasis on patient involvement in the therapeutic decision making process, it is important to identify and quantify any unforeseen risks of the conservation approach. One concern that has been raised is the question of radiation- related contralateral breast cancer after breast radiotherapy. Although most studies do not show statistically significant evidence that patients treated with breast radiotherapy are at increased risk of developing contralateral breast cancer when compared to control groups treated with mastectomy alone, there are clear data showing the amount of scattered radiation absorbed by the contralateral breast during a routine course of breast radiotherapy is considerable (several Gy) and is therefore within the range where one might be concerned about radiogenic contralateral tumors. While radiation related risks of contralateral breast cancer appear to be small enough to be statistically insignificant for the majority of patients, there may exist a smaller subset which, for genetic or environmental reasons, is at special risk for scatter related second tumors. If such a group could be predicted, it would seem appropriate to offer either special counselling or special prevention procedures aimed at mitigating this second tumor risk. The use of genetic testing, detailed analysis of breast cancer family history, and the identification of patients who acquired their first breast cancer at a very early age may all be candidate screening procedures useful in identifying such at- risk groups. Since some risk mitigation strategies are convenient and easy to utilize, it makes sense to follow the classic 'ALARA' (as low as reasonably

  8. UPDATING UNDER RISK CONDITION

    Directory of Open Access Journals (Sweden)

    VĂDUVA CECILIA ELENA

    2018-02-01

    Full Text Available The foundation for future firm development is investment. Agents have a risk aversion requiring higher returns as the risks associated with the project will be greater. The investment decision determines the market firm's affirmation, increasing the market share, dominating the market. Making an investment at a certain point will determine certain cash flows throughout the life of the project, and a residual value can be obtained when it is taken out of service. The flows and payments for the investment project can be more easily tracked if we are proposing a constant update rate. We will be able to analyze, based on various factors, three techniques for determining the discount rate for investment projects: the opportunity cost, the risk-free rate, and a series of risk premiums, the weighted average cost of capital. People without financial training make value judgments for investment projects based on other market opportunities, comparing the returns that any investment offers to other pay options. An investor has a sum of money he wants to make - if he does not invest in a project, he will invest in another, that will bring him a certain amount of money, choosing the most advantageous project by comparison. All projects are characterized by identical risks, and the agents are considered indifferent to the risks. The answer given by financial theory and practice to the disadvantage of rates in the opportunity cost category is the discount rate calculated as a sum of the risk-free rate and a risk premium, defining the risk as a factor whose action may cause a possible decrease in cash of the available flows. Higher objectivity is presented by the opportunity cost update rates of update because it refers to known variables but cannot be perfectly matched to the performance of the investment process.

  9. Comparative risk analysis

    International Nuclear Information System (INIS)

    Niehaus, F.

    1988-01-01

    In this paper, the risks of various energy systems are discussed considering severe accidents analysis, particularly the probabilistic safety analysis, and probabilistic safety criteria, and the applications of these criteria and analysis. The comparative risk analysis has demonstrated that the largest source of risk in every society is from daily small accidents. Nevertheless, we have to be more concerned about severe accidents. The comparative risk analysis of five different energy systems (coal, oil, gas, LWR and STEC (Solar)) for the public has shown that the main sources of risks are coal and oil. The latest comparative risk study of various energy has been conducted in the USA and has revealed that the number of victims from coal is 42 as many than victims from nuclear. A study for severe accidents from hydro-dams in United States has estimated the probability of dam failures at 1 in 10,000 years and the number of victims between 11,000 and 260,000. The average occupational risk from coal is one fatal accident in 1,000 workers/year. The probabilistic safety analysis is a method that can be used to assess nuclear energy risks, and to analyze the severe accidents, and to model all possible accident sequences and consequences. The 'Fault tree' analysis is used to know the probability of failure of the different systems at each point of accident sequences and to calculate the probability of risks. After calculating the probability of failure, the criteria for judging the numerical results have to be developed, that is the quantitative and qualitative goals. To achieve these goals, several systems have been devised by various countries members of AIEA. The probabilistic safety ana-lysis method has been developed by establishing a computer program permit-ting to know different categories of safety related information. 19 tabs. (author)

  10. Radiogenic risks from hysterosalpingography

    International Nuclear Information System (INIS)

    Perisinakis, Kostas; Damilakis, John; Theocharopoulos, Nicholas; Grammatikakis, John; Gourtsoyiannis, Nicholas

    2003-01-01

    The aim of this study was to determine ovarian dose, effective dose and associated radiogenic risks from hysterosalpingography (HSG), and to provide data for the estimation of radiogenic risks related to HSG studies performed in any laboratory. The fluoroscopy time, number of radiographs taken and entrance surface dose were measured in a series of 78 consecutive patients undergoing HSG as part of their infertility work-up. Organ-dose values per radiograph and per minute of fluoroscopy were separately determined using an anthropomorphic phantom and thermoluminescence dosimetry. The radiogenic risk for deleterious effects on a possible future embryo and the radiogenic risk for cancer induction on the patient undergoing HSG were estimated. The average HSG procedure in our laboratory involves a mean fluoroscopic time of 0.3 min and a mean number of radiographs of 3.2. The dose to female gonads from an average HSG procedure was 2.7 mGy and the patient effective dose was 1.2 mSv. The risk for radiogenic anomalies in a future embryo of the woman undergoing an average HSG procedure and the risk for radiogenic fatal cancer induction in the exposed woman were estimated to be less than 10 -3 of the correspondent nominal risks. Radiation risks from a typical HSG are low, but they may be elevated if fluoroscopic and/or radiographic exposures are prolonged for any reason. Present data allow the estimation of radiogenic risks associated with HSG procedures performed in other laboratories with use of different equipment, screening time and number of radiographs taken. (orig.)

  11. Risk in pediatric anesthesia.

    Science.gov (United States)

    Paterson, Neil; Waterhouse, Peter

    2011-08-01

    Risk in pediatric anesthesia can be conveniently classified as minor or major. Major morbidity includes cardiac arrest, brain damage and death. Minor morbidity can be assessed by clinical audits with small patient samples. Major morbidity is rare. It is best assessed by very large clinical studies and by review of closed malpractice claims. Both minor and major morbidity occur most commonly in infants and children under three, especially those with severe co-morbidities. Knowledge of risk profiles in pediatric anesthesia is a starting point for the reduction of risk. © 2010 Blackwell Publishing Ltd.

  12. Assessment of fracture risk

    International Nuclear Information System (INIS)

    Kanis, John A.; Johansson, Helena; Oden, Anders; McCloskey, Eugene V.

    2009-01-01

    Fractures are a common complication of osteoporosis. Although osteoporosis is defined by bone mineral density at the femoral neck, other sites and validated techniques can be used for fracture prediction. Several clinical risk factors contribute to fracture risk independently of BMD. These include age, prior fragility fracture, smoking, excess alcohol, family history of hip fracture, rheumatoid arthritis and the use of oral glucocorticoids. These risk factors in conjunction with BMD can be integrated to provide estimates of fracture probability using the FRAX tool. Fracture probability rather than BMD alone can be used to fashion strategies for the assessment and treatment of osteoporosis.

  13. Managing Risk and Opportunity

    DEFF Research Database (Denmark)

    Andersen, Torben Juul; Garvey, Maxine; Roggi, Oliviero

    outcomes. This topic is timely and of interest both to the academic community as well as to practicing managers, executives, and directors. The volume focuses on contemporary risk leadership issues based on recent research insights but avoids excessive technical language and mathematical formulas. The book...... is framed around the challenges imposed on executives and directors in dealing with an increasingly complex and unpredictable world. This requires a new risk leadership focus that not only avoids the downside risks but also considers ways to exploit the upside potential offered by a dynamic environment...

  14. PREVENTION OF COMPANY RISKS

    Directory of Open Access Journals (Sweden)

    SUCI U GHEORGHE

    2014-10-01

    Full Text Available A company’s manager has to create and maintain a healthy internal control system. An efficient internal control system implies the implementation in the company of risk management. Each company, but also each individual, who tries to attain certain objectives, establishes the activities which lead to the achievement of goals and, at the same time, tries to identify as many “threats” as possible, in order to take the necessary measures to eliminate them. Thus, even if one is not familiar with the concepts of risk and risk management, one acts, consciously or not, for that purpose.

  15. Credit Risk Modeling

    DEFF Research Database (Denmark)

    Lando, David

    Credit risk is today one of the most intensely studied topics in quantitative finance. This book provides an introduction and overview for readers who seek an up-to-date reference to the central problems of the field and to the tools currently used to analyze them. The book is aimed at researchers...... and students in finance, at quantitative analysts in banks and other financial institutions, and at regulators interested in the modeling aspects of credit risk. David Lando considers the two broad approaches to credit risk analysis: that based on classical option pricing models on the one hand...

  16. Social identities and risk

    DEFF Research Database (Denmark)

    Blok, Anders; Jensen, Mette; Kaltoft, Pernille

    2008-01-01

    Expert-based environmental and health risk regulation is widely believed to suffer from a lack of public understanding and legitimacy. On controversial issues such as genetically modified organisms and food-related chemicals, a "lay-expert discrepancy" in the assessment of risks is clearly visible...... of social identities. On the basis of qualitative interviews with citizens and experts, respectively, we focus on the multiple ways in which identities come to be employed in actors' risk accounts. Empirically, we identify salient characteristics of "typical" imagined experts and lay-people, while arguing...

  17. riskRegression

    DEFF Research Database (Denmark)

    Ozenne, Brice; Sørensen, Anne Lyngholm; Scheike, Thomas

    2017-01-01

    In the presence of competing risks a prediction of the time-dynamic absolute risk of an event can be based on cause-specific Cox regression models for the event and the competing risks (Benichou and Gail, 1990). We present computationally fast and memory optimized C++ functions with an R interface......-product we obtain fast access to the baseline hazards (compared to survival::basehaz()) and predictions of survival probabilities, their confidence intervals and confidence bands. Confidence intervals and confidence bands are based on point-wise asymptotic expansions of the corresponding statistical...

  18. Some thoughts about risk

    International Nuclear Information System (INIS)

    Jennekens, J.H.

    1986-05-01

    The author discusses how the concept of risk is perceived differently by the scientist and the man in the street, and mentions the problems that this can sometimes pose for the regulator. He also gives examples of inconsistencies and contradictions in various areas of risk management. He concludes by noting that so-called accidents usually do not occur by chance, but that system or component failures are always due to some form of human error. The objective of risk management is to ensure, by a process of rigorous analysis, that both the probability and consequences of such failures are minimized

  19. Alternative Perspectives on Risk

    Science.gov (United States)

    Davison, Jeannie; Orasanu, J.; Connors, Mary M. (Technical Monitor)

    1997-01-01

    The goal of the commercial air transport system is to provide air transportation to the flying public at an acceptable cost with minimal risk. in an ideal situation these three goals would support each other. In fact, it is sometimes the case that the goals conflict: getting passengers to their destinations on time may conflict with fixing a minor mechanical malfunction that may or may not impact safety; flying a route that will avoid turbulence, thereby providing passengers with a more comfortable ride, may consume more fuel; managing traffic density may mean aircraft are delayed or must use an approach that will result in a long taxi to their gates, costing time and fuel. Various players in the system--pilots, dispatchers, controllers, as well as managers in the airline carriers and traffic management system--make decisions every day that involve trade-offs of benefits and costs. The prospect of revisions in the air traffic management system, with shifts in responsibilities from controllers to users, including airline operations center personnel and pilots, means that individuals may be performing either new jobs or old jobs under new guidance. It will be essential to know how the various players (a) perceive the risks and benefits associated with the decisions they will make under the old and new control structures, and (b) how much risk they are willing to accept in making decisions. Risk is here defined as the probability and magnitude of negative events (after Slovic, 1987). Of primary interest are risks associated with traffic, weather, and operational factors such as schedule, fuel consumption, and passenger service. Previous research has documented differences between groups in perceptions of risks associated with both everyday and aviation related situations. Risk perception varies as a function of familiarity with the situation, degree to which one is potentially affected by the risk, the level of control one has over the situation, and one's level of

  20. Governmental management of chemical risk

    International Nuclear Information System (INIS)

    Zimmerman, R.

    1990-01-01

    This book is organized under the following headings: risk management in the government context; legal and regulatory decrees and directives for managing chemical risk; incentive-based approaches for regulating risk; risk management in the federal system; and traditional approaches and new initiatives for managing chemical risk